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We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)","type":"research_data","date_published":"2023-08-04T00:00:00Z","doi":"10.15479/AT:ISTA:13126","citation":{"short":"J.G. Danzl, (2023).","ama":"Danzl JG. Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>","ista":"Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>.","ieee":"J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023.","chicago":"Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.’” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">https://doi.org/10.15479/AT:ISTA:13126</a>.","mla":"Danzl, Johann G. <i>Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.”</i> Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>.","apa":"Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. <a 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Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"month":"08","article_processing_charge":"No","status":"public","related_material":{"record":[{"status":"public","id":"14257","relation":"used_in_publication"}],"link":[{"url":"https://pub.ista.ac.at/group_danzl/data/CATS/","description":"Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. ","relation":"research_data"}]}},{"intvolume":"        29","year":"2023","acknowledgement":"This work received support from the European Union-funded Horizon Europe project ‘environMENTAL’ (no. 101057429 to G.S., A.M. and M.M.N.) and cofunding by UK Research and Innovation under the UK Government’s Horizon Europe funding guarantee (nos. 10041392 and 10038599) for study design and data analysis; the Horizon 2020-funded European Research Council Advanced Grant ‘STRATIFY’ (no. 695313 to G.S. for study design and data analysis); the Human Brain Project (HBP SGA3, no. 945539 to G.S. for study design and data analysis); the National Institutes of Health (grant no. R01DA049238 to G.S. for study design and data analysis); the German Research Foundation (COPE; grant no. 675346 to G.S. for study design and data analysis); the National Natural Science Foundation of China (grant no. 82001797 to J.X., grant no. 82030053 to C.Y., grant no. 82202093 to J.T. and grant no. 82150710554 to G.S. for study design, data analysis and preparation of the manuscript); National Key Research and Development Program of China (grant no. 2018YFC1314301 to C.Y. for study design and data analysis); Tianjin Applied Basic Research Diversified Investment Foundation (grant no. 21JCYBJC01360 to J.X. for study design and data analysis); Tianjin Health Technology Project (grant no. TJWJ2021QN002 to J.X. for preparation of the manuscript); Science & Technology Development Fund of the Tianjin Education Commission for Higher Education (grant no. 2019KJ195 to J.X. for preparation of the manuscript); the Tianjin Medical University ‘Clinical Talent Training 123 Climbing Plan’ to J.X. for the preparation of the manuscript; Tianjin Key Medical Discipline (Specialty) Construction Project (grant no. TJYXZDXK-001A to C.Y. for preparation of the manuscript); the National Key R&D Program of China (grant no. 2022YFE0209400 to L.Y. for study design and data analysis); the Tsinghua University Initiative Scientific Research Program (grant no. 2021Z11GHX002 to L.Y. for study design and data analysis); the National Key Scientific and Technological Infrastructure Project ‘Earth System Science Numerical Simulator Facility’ (EarthLab to L.Y. for study design and data analysis); the Chinese National High-end Foreign Expert Recruitment Plan to G.S.; and the Alexander von Humboldt Foundation to G.S. for study design and data analysis.","publication_identifier":{"eissn":["1546-170X"],"issn":["1078-8956"]},"title":"Effects of urban living environments on mental health in adults","doi":"10.1038/s41591-023-02365-w","type":"journal_article","date_published":"2023-06-15T00:00:00Z","language":[{"iso":"eng"}],"publication":"Nature Medicine","scopus_import":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_created":"2023-06-25T22:00:46Z","article_type":"original","citation":{"ista":"Xu J, Liu N, Polemiti E, Garcia-Mondragon L, Tang J, Liu X, Lett T, Yu L, Nöthen MM, Feng J, Yu C, Marquand A, Schumann G, Walter H, Heinz A, Ralser M, Twardziok S, Vaidya N, Serin E, Jentsch M, Hitchen E, Eils R, Taron UH, Schütz T, Schepanski K, Banks J, Banaschewski T, Jansone K, Christmann N, Meyer-Lindenberg A, Tost H, Holz N, Schwarz E, Stringaris A, Neidhart M, Nees F, Siehl S, A. Andreassen O, T. Westlye L, Van Der Meer D, Fernandez S, Kjelkenes R, Ask H, Rapp M, Tschorn M, Böttger SJ, Novarino G, Marr L, Slater M, Viapiana GF, Orosa FE, Gallego J, Pastor A, Forstner A, Hoffmann P, M. Nöthen M, J. Forstner A, Claus I, Miller A, Heilmann-Heimbach S, Sommer P, Boye M, Wilbertz J, Schmitt K, Jirsa V, Petkoski S, Pitel S, Otten L, Athanasiadis AP, Pearmund C, Spanlang B, Alvarez E, Sanchez M, Giner A, Hese S, Renner P, Jia T, Gong Y, Xia Y, Chang X, Calhoun V, Liu J, Thompson P, Clinton N, Desrivieres S, H. Young A, Stahl B, Ogoh G. 2023. Effects of urban living environments on mental health in adults. Nature Medicine. 29, 1456–1467.","ieee":"J. Xu <i>et al.</i>, “Effects of urban living environments on mental health in adults,” <i>Nature Medicine</i>, vol. 29. Springer Nature, pp. 1456–1467, 2023.","chicago":"Xu, Jiayuan, Nana Liu, Elli Polemiti, Liliana Garcia-Mondragon, Jie Tang, Xiaoxuan Liu, Tristram Lett, et al. “Effects of Urban Living Environments on Mental Health in Adults.” <i>Nature Medicine</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41591-023-02365-w\">https://doi.org/10.1038/s41591-023-02365-w</a>.","mla":"Xu, Jiayuan, et al. “Effects of Urban Living Environments on Mental Health in Adults.” <i>Nature Medicine</i>, vol. 29, Springer Nature, 2023, pp. 1456–67, doi:<a href=\"https://doi.org/10.1038/s41591-023-02365-w\">10.1038/s41591-023-02365-w</a>.","apa":"Xu, J., Liu, N., Polemiti, E., Garcia-Mondragon, L., Tang, J., Liu, X., … Ogoh, G. (2023). Effects of urban living environments on mental health in adults. <i>Nature Medicine</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41591-023-02365-w\">https://doi.org/10.1038/s41591-023-02365-w</a>","short":"J. Xu, N. Liu, E. Polemiti, L. Garcia-Mondragon, J. Tang, X. Liu, T. Lett, L. Yu, M.M. Nöthen, J. Feng, C. Yu, A. Marquand, G. Schumann, H. Walter, A. Heinz, M. Ralser, S. Twardziok, N. Vaidya, E. Serin, M. Jentsch, E. Hitchen, R. Eils, U.H. Taron, T. Schütz, K. Schepanski, J. Banks, T. Banaschewski, K. Jansone, N. Christmann, A. Meyer-Lindenberg, H. Tost, N. Holz, E. Schwarz, A. Stringaris, M. Neidhart, F. Nees, S. Siehl, O. A. Andreassen, L. T. Westlye, D. Van Der Meer, S. Fernandez, R. Kjelkenes, H. Ask, M. Rapp, M. Tschorn, S.J. Böttger, G. Novarino, L. Marr, M. Slater, G.F. Viapiana, F.E. Orosa, J. Gallego, A. Pastor, A. Forstner, P. Hoffmann, M. M. Nöthen, A. J. Forstner, I. Claus, A. Miller, S. Heilmann-Heimbach, P. Sommer, M. Boye, J. Wilbertz, K. Schmitt, V. Jirsa, S. Petkoski, S. Pitel, L. Otten, A.P. Athanasiadis, C. Pearmund, B. Spanlang, E. Alvarez, M. Sanchez, A. Giner, S. Hese, P. Renner, T. Jia, Y. Gong, Y. Xia, X. Chang, V. Calhoun, J. Liu, P. Thompson, N. Clinton, S. Desrivieres, A. H. Young, B. Stahl, G. Ogoh, Nature Medicine 29 (2023) 1456–1467.","ama":"Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental health in adults. <i>Nature Medicine</i>. 2023;29:1456-1467. doi:<a href=\"https://doi.org/10.1038/s41591-023-02365-w\">10.1038/s41591-023-02365-w</a>"},"file":[{"access_level":"open_access","date_created":"2023-06-26T10:15:44Z","creator":"dernst","relation":"main_file","file_id":"13171","success":1,"checksum":"bcd3225b2731c3442fa98987fd3bd46d","content_type":"application/pdf","file_name":"2023_NatureMedicine_Xu.pdf","date_updated":"2023-06-26T10:15:44Z","file_size":7365360}],"oa_version":"Published Version","status":"public","department":[{"_id":"GaNo"}],"month":"06","volume":29,"isi":1,"abstract":[{"lang":"eng","text":"Urban-living individuals are exposed to many environmental factors that may combine and interact to influence mental health. While individual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city relates to brain and mental health, and how this is moderated by genetic factors. Using the data of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation analyses to investigate the relationships between urban environments and psychiatric symptoms. We found an environmental profile of social deprivation, air pollution, street network and urban land-use density that was positively correlated with an affective symptom group (r = 0.22, Pperm < 0.001), mediated by brain volume differences consistent with reward processing, and moderated by genes enriched for stress response, including CRHR1, explaining 2.01% of the variance in brain volume differences. Protective factors such as greenness and generous destination accessibility were negatively correlated with an anxiety symptom group (r = 0.10, Pperm < 0.001), mediated by brain regions necessary for emotion regulation and moderated by EXD3, explaining 1.65% of the variance. The third urban environmental profile was correlated with an emotional instability symptom group (r = 0.03, Pperm < 0.001). Our findings suggest that different environmental profiles of urban living may influence specific psychiatric symptom groups through distinct neurobiological pathways."}],"article_processing_charge":"No","day":"15","external_id":{"isi":["001013172700001"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"1456-1467","date_updated":"2023-12-13T11:25:55Z","oa":1,"file_date_updated":"2023-06-26T10:15:44Z","publisher":"Springer Nature","has_accepted_license":"1","ddc":["570"],"author":[{"first_name":"Jiayuan","full_name":"Xu, Jiayuan","last_name":"Xu"},{"first_name":"Nana","full_name":"Liu, Nana","last_name":"Liu"},{"last_name":"Polemiti","full_name":"Polemiti, Elli","first_name":"Elli"},{"first_name":"Liliana","last_name":"Garcia-Mondragon","full_name":"Garcia-Mondragon, Liliana"},{"full_name":"Tang, Jie","last_name":"Tang","first_name":"Jie"},{"first_name":"Xiaoxuan","full_name":"Liu, Xiaoxuan","last_name":"Liu"},{"full_name":"Lett, Tristram","last_name":"Lett","first_name":"Tristram"},{"first_name":"Le","last_name":"Yu","full_name":"Yu, Le"},{"first_name":"Markus M.","full_name":"Nöthen, Markus M.","last_name":"Nöthen"},{"full_name":"Feng, Jianfeng","last_name":"Feng","first_name":"Jianfeng"},{"first_name":"Chunshui","full_name":"Yu, Chunshui","last_name":"Yu"},{"first_name":"Andre","full_name":"Marquand, Andre","last_name":"Marquand"},{"first_name":"Gunter","full_name":"Schumann, Gunter","last_name":"Schumann"},{"first_name":"Henrik","last_name":"Walter","full_name":"Walter, Henrik"},{"first_name":"Andreas","full_name":"Heinz, Andreas","last_name":"Heinz"},{"full_name":"Ralser, Markus","last_name":"Ralser","first_name":"Markus"},{"full_name":"Twardziok, Sven","last_name":"Twardziok","first_name":"Sven"},{"first_name":"Nilakshi","full_name":"Vaidya, Nilakshi","last_name":"Vaidya"},{"first_name":"Emin","last_name":"Serin","full_name":"Serin, Emin"},{"first_name":"Marcel","last_name":"Jentsch","full_name":"Jentsch, Marcel"},{"first_name":"Esther","full_name":"Hitchen, Esther","last_name":"Hitchen"},{"first_name":"Roland","last_name":"Eils","full_name":"Eils, Roland"},{"last_name":"Taron","full_name":"Taron, Ulrike Helene","first_name":"Ulrike Helene"},{"first_name":"Tatjana","last_name":"Schütz","full_name":"Schütz, Tatjana"},{"first_name":"Kerstin","full_name":"Schepanski, Kerstin","last_name":"Schepanski"},{"last_name":"Banks","full_name":"Banks, Jamie","first_name":"Jamie"},{"first_name":"Tobias","last_name":"Banaschewski","full_name":"Banaschewski, Tobias"},{"first_name":"Karina","full_name":"Jansone, Karina","last_name":"Jansone"},{"full_name":"Christmann, Nina","last_name":"Christmann","first_name":"Nina"},{"full_name":"Meyer-Lindenberg, Andreas","last_name":"Meyer-Lindenberg","first_name":"Andreas"},{"first_name":"Heike","full_name":"Tost, Heike","last_name":"Tost"},{"first_name":"Nathalie","full_name":"Holz, Nathalie","last_name":"Holz"},{"first_name":"Emanuel","full_name":"Schwarz, Emanuel","last_name":"Schwarz"},{"first_name":"Argyris","full_name":"Stringaris, Argyris","last_name":"Stringaris"},{"first_name":"Maja","last_name":"Neidhart","full_name":"Neidhart, Maja"},{"first_name":"Frauke","last_name":"Nees","full_name":"Nees, Frauke"},{"first_name":"Sebastian","full_name":"Siehl, Sebastian","last_name":"Siehl"},{"first_name":"Ole","full_name":"A. Andreassen, Ole","last_name":"A. Andreassen"},{"last_name":"T. Westlye","full_name":"T. Westlye, Lars","first_name":"Lars"},{"last_name":"Van Der Meer","full_name":"Van Der Meer, Dennis","first_name":"Dennis"},{"first_name":"Sara","last_name":"Fernandez","full_name":"Fernandez, Sara"},{"full_name":"Kjelkenes, Rikka","last_name":"Kjelkenes","first_name":"Rikka"},{"first_name":"Helga","full_name":"Ask, Helga","last_name":"Ask"},{"first_name":"Michael","last_name":"Rapp","full_name":"Rapp, Michael"},{"first_name":"Mira","full_name":"Tschorn, Mira","last_name":"Tschorn"},{"first_name":"Sarah Jane","full_name":"Böttger, Sarah Jane","last_name":"Böttger"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178"},{"last_name":"Marr","full_name":"Marr, Lena","first_name":"Lena","id":"4406F586-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Slater","full_name":"Slater, Mel","first_name":"Mel"},{"last_name":"Viapiana","full_name":"Viapiana, Guillem Feixas","first_name":"Guillem Feixas"},{"last_name":"Orosa","full_name":"Orosa, Francisco Eiroa","first_name":"Francisco Eiroa"},{"full_name":"Gallego, Jaime","last_name":"Gallego","first_name":"Jaime"},{"last_name":"Pastor","full_name":"Pastor, Alvaro","first_name":"Alvaro"},{"first_name":"Andreas","last_name":"Forstner","full_name":"Forstner, Andreas"},{"first_name":"Per","full_name":"Hoffmann, Per","last_name":"Hoffmann"},{"full_name":"M. Nöthen, Markus","last_name":"M. Nöthen","first_name":"Markus"},{"last_name":"J. Forstner","full_name":"J. Forstner, Andreas","first_name":"Andreas"},{"last_name":"Claus","full_name":"Claus, Isabelle","first_name":"Isabelle"},{"full_name":"Miller, Abbi","last_name":"Miller","first_name":"Abbi"},{"first_name":"Stefanie","full_name":"Heilmann-Heimbach, Stefanie","last_name":"Heilmann-Heimbach"},{"last_name":"Sommer","full_name":"Sommer, Peter","first_name":"Peter"},{"full_name":"Boye, Mona","last_name":"Boye","first_name":"Mona"},{"full_name":"Wilbertz, Johannes","last_name":"Wilbertz","first_name":"Johannes"},{"first_name":"Karen","last_name":"Schmitt","full_name":"Schmitt, Karen"},{"first_name":"Viktor","last_name":"Jirsa","full_name":"Jirsa, Viktor"},{"last_name":"Petkoski","full_name":"Petkoski, Spase","first_name":"Spase"},{"first_name":"Séverine","full_name":"Pitel, Séverine","last_name":"Pitel"},{"last_name":"Otten","full_name":"Otten, Lisa","first_name":"Lisa"},{"full_name":"Athanasiadis, Anastasios Polykarpos","last_name":"Athanasiadis","first_name":"Anastasios Polykarpos"},{"last_name":"Pearmund","full_name":"Pearmund, Charlie","first_name":"Charlie"},{"full_name":"Spanlang, Bernhard","last_name":"Spanlang","first_name":"Bernhard"},{"full_name":"Alvarez, Elena","last_name":"Alvarez","first_name":"Elena"},{"first_name":"Mavi","full_name":"Sanchez, Mavi","last_name":"Sanchez"},{"first_name":"Arantxa","full_name":"Giner, Arantxa","last_name":"Giner"},{"first_name":"Sören","last_name":"Hese","full_name":"Hese, Sören"},{"first_name":"Paul","full_name":"Renner, Paul","last_name":"Renner"},{"full_name":"Jia, Tianye","last_name":"Jia","first_name":"Tianye"},{"last_name":"Gong","full_name":"Gong, Yanting","first_name":"Yanting"},{"first_name":"Yunman","full_name":"Xia, Yunman","last_name":"Xia"},{"last_name":"Chang","full_name":"Chang, Xiao","first_name":"Xiao"},{"full_name":"Calhoun, Vince","last_name":"Calhoun","first_name":"Vince"},{"last_name":"Liu","full_name":"Liu, Jingyu","first_name":"Jingyu"},{"full_name":"Thompson, Paul","last_name":"Thompson","first_name":"Paul"},{"full_name":"Clinton, Nicholas","last_name":"Clinton","first_name":"Nicholas"},{"first_name":"Sylvane","last_name":"Desrivieres","full_name":"Desrivieres, Sylvane"},{"first_name":"Allan","last_name":"H. Young","full_name":"H. Young, Allan"},{"full_name":"Stahl, Bernd","last_name":"Stahl","first_name":"Bernd"},{"first_name":"George","full_name":"Ogoh, George","last_name":"Ogoh"}],"_id":"13168","publication_status":"published","quality_controlled":"1"},{"related_material":{"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}],"record":[{"status":"public","id":"12817","relation":"research_data"},{"relation":"shorter_version","id":"14770","status":"public"},{"relation":"earlier_version","id":"11943","status":"public"},{"id":"18674","status":"public","relation":"dissertation_contains"}]},"status":"public","abstract":[{"text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue.","lang":"eng"}],"month":"08","volume":20,"isi":1,"article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"ec_funded":1,"date_created":"2023-07-23T22:01:13Z","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file":[{"relation":"main_file","date_created":"2025-02-26T08:01:57Z","creator":"dernst","file_id":"19088","access_level":"open_access","date_updated":"2025-02-26T08:01:57Z","file_name":"2023_NatureMethods_Velicky.pdf","file_size":14103039,"content_type":"application/pdf","success":1,"checksum":"a68e845780a82ea36d0d4d3212a87c10"}],"oa_version":"Published Version","citation":{"ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265."},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"OA_place":"publisher","doi":"10.1038/s41592-023-01936-6","date_published":"2023-08-01T00:00:00Z","language":[{"iso":"eng"}],"publication":"Nature Methods","scopus_import":"1","type":"journal_article","acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","intvolume":"        20","year":"2023","title":"Dense 4D nanoscale reconstruction of living brain tissue","publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"pmid":1,"publication_status":"published","quality_controlled":"1","corr_author":"1","file_date_updated":"2025-02-26T08:01:57Z","oa":1,"ddc":["570"],"has_accepted_license":"1","author":[{"full_name":"Velicky, Philipp","last_name":"Velicky","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp"},{"id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder","orcid":"0000-0001-5665-0430","last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder"},{"full_name":"Michalska, Julia M","last_name":"Michalska","orcid":"0000-0003-3862-1235","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"first_name":"Donglai","full_name":"Wei, Donglai","last_name":"Wei"},{"full_name":"Lin, Zudi","last_name":"Lin","first_name":"Zudi"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake"},{"first_name":"Jakob","full_name":"Troidl, Jakob","last_name":"Troidl"},{"last_name":"Beyer","full_name":"Beyer, Johanna","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","last_name":"Ben Simon","full_name":"Ben Simon, Yoav"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"orcid":"0000-0003-0201-2315","last_name":"Jahr","full_name":"Jahr, Wiebke","first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"last_name":"Broichhagen","full_name":"Broichhagen, Johannes","first_name":"Johannes"},{"first_name":"Seth G.N.","last_name":"Grant","full_name":"Grant, Seth G.N."},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"full_name":"Novarino, Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"first_name":"Hanspeter","full_name":"Pfister, Hanspeter","last_name":"Pfister"},{"first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","full_name":"Bickel, Bernd","last_name":"Bickel","orcid":"0000-0001-6511-9385"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"_id":"13267","publisher":"Springer Nature","date_updated":"2026-04-07T12:58:30Z","page":"1256-1265","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"01","external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"OA_type":"hybrid","project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232","call_identifier":"FWF"},{"grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E","grant_number":"LS18-022"},{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"call_identifier":"H2020","_id":"24F9549A-B435-11E9-9278-68D0E5697425","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","grant_number":"715767"},{"call_identifier":"H2020","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020"},{"grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}]},{"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","external_id":{"isi":["001093447000016"],"pmid":["37610741"]},"day":"01","date_updated":"2025-09-09T13:11:20Z","page":"1066-1074","_id":"14443","author":[{"full_name":"Schumann, Gunter","last_name":"Schumann","first_name":"Gunter"},{"first_name":"Ole A.","last_name":"Andreassen","full_name":"Andreassen, Ole A."},{"full_name":"Banaschewski, Tobias","last_name":"Banaschewski","first_name":"Tobias"},{"first_name":"Vince D.","full_name":"Calhoun, Vince D.","last_name":"Calhoun"},{"first_name":"Nicholas","full_name":"Clinton, Nicholas","last_name":"Clinton"},{"last_name":"Desrivieres","full_name":"Desrivieres, Sylvane","first_name":"Sylvane"},{"full_name":"Brandlistuen, Ragnhild Eek","last_name":"Brandlistuen","first_name":"Ragnhild Eek"},{"full_name":"Feng, Jianfeng","last_name":"Feng","first_name":"Jianfeng"},{"first_name":"Soeren","full_name":"Hese, Soeren","last_name":"Hese"},{"last_name":"Hitchen","full_name":"Hitchen, Esther","first_name":"Esther"},{"last_name":"Hoffmann","full_name":"Hoffmann, Per","first_name":"Per"},{"first_name":"Tianye","full_name":"Jia, Tianye","last_name":"Jia"},{"full_name":"Jirsa, Viktor","last_name":"Jirsa","first_name":"Viktor"},{"first_name":"Andre F.","full_name":"Marquand, Andre F.","last_name":"Marquand"},{"last_name":"Nees","full_name":"Nees, Frauke","first_name":"Frauke"},{"first_name":"Markus M.","full_name":"Nöthen, Markus M.","last_name":"Nöthen"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"full_name":"Polemiti, Elli","last_name":"Polemiti","first_name":"Elli"},{"first_name":"Markus","full_name":"Ralser, Markus","last_name":"Ralser"},{"last_name":"Rapp","full_name":"Rapp, Michael","first_name":"Michael"},{"full_name":"Schepanski, Kerstin","last_name":"Schepanski","first_name":"Kerstin"},{"last_name":"Schikowski","full_name":"Schikowski, Tamara","first_name":"Tamara"},{"full_name":"Slater, Mel","last_name":"Slater","first_name":"Mel"},{"first_name":"Peter","last_name":"Sommer","full_name":"Sommer, Peter"},{"first_name":"Bernd Carsten","full_name":"Stahl, Bernd Carsten","last_name":"Stahl"},{"first_name":"Paul M.","full_name":"Thompson, Paul M.","last_name":"Thompson"},{"first_name":"Sven","last_name":"Twardziok","full_name":"Twardziok, Sven"},{"first_name":"Dennis","full_name":"Van Der Meer, Dennis","last_name":"Van Der Meer"},{"first_name":"Henrik","full_name":"Walter, Henrik","last_name":"Walter"},{"last_name":"Westlye","full_name":"Westlye, Lars","first_name":"Lars"}],"publisher":"American Medical Association","quality_controlled":"1","publication_status":"published","title":"Addressing global environmental challenges to mental health using population neuroscience: A review","pmid":1,"publication_identifier":{"eissn":["2168-6238"]},"issue":"10","year":"2023","intvolume":"        80","scopus_import":"1","language":[{"iso":"eng"}],"date_published":"2023-10-01T00:00:00Z","publication":"JAMA Psychiatry","type":"journal_article","doi":"10.1001/jamapsychiatry.2023.2996","oa_version":"None","citation":{"ama":"Schumann G, Andreassen OA, Banaschewski T, et al. Addressing global environmental challenges to mental health using population neuroscience: A review. <i>JAMA Psychiatry</i>. 2023;80(10):1066-1074. doi:<a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">10.1001/jamapsychiatry.2023.2996</a>","short":"G. Schumann, O.A. Andreassen, T. Banaschewski, V.D. Calhoun, N. Clinton, S. Desrivieres, R.E. Brandlistuen, J. Feng, S. Hese, E. Hitchen, P. Hoffmann, T. Jia, V. Jirsa, A.F. Marquand, F. Nees, M.M. Nöthen, G. Novarino, E. Polemiti, M. Ralser, M. Rapp, K. Schepanski, T. Schikowski, M. Slater, P. Sommer, B.C. Stahl, P.M. Thompson, S. Twardziok, D. Van Der Meer, H. Walter, L. Westlye, JAMA Psychiatry 80 (2023) 1066–1074.","ieee":"G. Schumann <i>et al.</i>, “Addressing global environmental challenges to mental health using population neuroscience: A review,” <i>JAMA Psychiatry</i>, vol. 80, no. 10. American Medical Association, pp. 1066–1074, 2023.","ista":"Schumann G, Andreassen OA, Banaschewski T, Calhoun VD, Clinton N, Desrivieres S, Brandlistuen RE, Feng J, Hese S, Hitchen E, Hoffmann P, Jia T, Jirsa V, Marquand AF, Nees F, Nöthen MM, Novarino G, Polemiti E, Ralser M, Rapp M, Schepanski K, Schikowski T, Slater M, Sommer P, Stahl BC, Thompson PM, Twardziok S, Van Der Meer D, Walter H, Westlye L. 2023. Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. 80(10), 1066–1074.","mla":"Schumann, Gunter, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” <i>JAMA Psychiatry</i>, vol. 80, no. 10, American Medical Association, 2023, pp. 1066–74, doi:<a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">10.1001/jamapsychiatry.2023.2996</a>.","apa":"Schumann, G., Andreassen, O. A., Banaschewski, T., Calhoun, V. D., Clinton, N., Desrivieres, S., … Westlye, L. (2023). Addressing global environmental challenges to mental health using population neuroscience: A review. <i>JAMA Psychiatry</i>. American Medical Association. <a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">https://doi.org/10.1001/jamapsychiatry.2023.2996</a>","chicago":"Schumann, Gunter, Ole A. Andreassen, Tobias Banaschewski, Vince D. Calhoun, Nicholas Clinton, Sylvane Desrivieres, Ragnhild Eek Brandlistuen, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” <i>JAMA Psychiatry</i>. American Medical Association, 2023. <a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">https://doi.org/10.1001/jamapsychiatry.2023.2996</a>."},"article_type":"review","date_created":"2023-10-22T22:01:14Z","article_processing_charge":"No","month":"10","abstract":[{"lang":"eng","text":"Importance  Climate change, pollution, urbanization, socioeconomic inequality, and psychosocial effects of the COVID-19 pandemic have caused massive changes in environmental conditions that affect brain health during the life span, both on a population level as well as on the level of the individual. How these environmental factors influence the brain, behavior, and mental illness is not well known.\r\nObservations  A research strategy enabling population neuroscience to contribute to identify brain mechanisms underlying environment-related mental illness by leveraging innovative enrichment tools for data federation, geospatial observation, climate and pollution measures, digital health, and novel data integration techniques is described. This strategy can inform innovative treatments that target causal cognitive and molecular mechanisms of mental illness related to the environment. An example is presented of the environMENTAL Project that is leveraging federated cohort data of over 1.5 million European citizens and patients enriched with deep phenotyping data from large-scale behavioral neuroimaging cohorts to identify brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress, and substance misuse.\r\nConclusions and Relevance  This research will lead to the development of objective biomarkers and evidence-based interventions that will significantly improve outcomes of environment-related mental illness."}],"isi":1,"volume":80,"department":[{"_id":"GaNo"}],"status":"public"},{"citation":{"short":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry 14 (2023).","ama":"Narzisi A, Halladay A, Masi G, Novarino G, Lord C. Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. <i>Frontiers in Psychiatry</i>. 2023;14. doi:<a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">10.3389/fpsyt.2023.1287879</a>","chicago":"Narzisi, Antonio, Alycia Halladay, Gabriele Masi, Gaia Novarino, and Catherine Lord. “Tempering Expectations: Considerations on the Current State of Stem Cells Therapy for Autism Treatment.” <i>Frontiers in Psychiatry</i>. Frontiers, 2023. <a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">https://doi.org/10.3389/fpsyt.2023.1287879</a>.","mla":"Narzisi, Antonio, et al. “Tempering Expectations: Considerations on the Current State of Stem Cells Therapy for Autism Treatment.” <i>Frontiers in Psychiatry</i>, vol. 14, 1287879, Frontiers, 2023, doi:<a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">10.3389/fpsyt.2023.1287879</a>.","apa":"Narzisi, A., Halladay, A., Masi, G., Novarino, G., &#38; Lord, C. (2023). Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. <i>Frontiers in Psychiatry</i>. Frontiers. <a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">https://doi.org/10.3389/fpsyt.2023.1287879</a>","ista":"Narzisi A, Halladay A, Masi G, Novarino G, Lord C. 2023. Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. Frontiers in Psychiatry. 14, 1287879.","ieee":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, and C. Lord, “Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment,” <i>Frontiers in Psychiatry</i>, vol. 14. Frontiers, 2023."},"file":[{"file_id":"14468","relation":"main_file","creator":"dernst","date_created":"2023-10-30T12:48:40Z","access_level":"open_access","file_name":"2023_FrontiersPsychiatry_Narzisi.pdf","file_size":147878,"date_updated":"2023-10-30T12:48:40Z","content_type":"application/pdf","checksum":"0a76373e9a4c0fc199f80380de257e86","success":1}],"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"letter_note","date_created":"2023-10-29T23:01:16Z","department":[{"_id":"GaNo"}],"volume":14,"month":"10","isi":1,"article_processing_charge":"Yes","status":"public","publication_identifier":{"eissn":["1664-0640"]},"article_number":"1287879","pmid":1,"title":"Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment","intvolume":"        14","year":"2023","acknowledgement":"The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work has been partially supported by Italian Ministry of Health Grant RC2023 (and the 5 × 1,000 voluntary contributions). The authors thank the children and their families with whom they work daily.","type":"journal_article","publication":"Frontiers in Psychiatry","date_published":"2023-10-03T00:00:00Z","language":[{"iso":"eng"}],"scopus_import":"1","doi":"10.3389/fpsyt.2023.1287879","publisher":"Frontiers","has_accepted_license":"1","ddc":["570"],"_id":"14455","author":[{"last_name":"Narzisi","full_name":"Narzisi, Antonio","first_name":"Antonio"},{"full_name":"Halladay, Alycia","last_name":"Halladay","first_name":"Alycia"},{"first_name":"Gabriele","last_name":"Masi","full_name":"Masi, Gabriele"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"first_name":"Catherine","full_name":"Lord, Catherine","last_name":"Lord"}],"oa":1,"file_date_updated":"2023-10-30T12:48:40Z","quality_controlled":"1","publication_status":"published","day":"03","external_id":{"isi":["001084841700001"],"pmid":["37854442"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2023-12-13T13:06:07Z"},{"date_created":"2022-03-04T08:53:37Z","article_type":"original","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png"},"file":[{"file_size":5340294,"file_name":"2021_Glia_Basilico.pdf","date_updated":"2022-03-04T08:55:27Z","content_type":"application/pdf","success":1,"checksum":"f10a897290e66c0a062e04ba91db6c17","relation":"main_file","creator":"dernst","date_created":"2022-03-04T08:55:27Z","file_id":"10819","access_level":"open_access"}],"oa_version":"Published Version","citation":{"ieee":"B. Basilico <i>et al.</i>, “Microglia control glutamatergic synapses in the adult mouse hippocampus,” <i>Glia</i>, vol. 70, no. 1. Wiley, pp. 173–195, 2022.","ista":"Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, Ferretti V, Reverte I, Sanchini C, Marrone MC, Giubettini M, De Turris V, Salerno D, Garofalo S, St‐Pierre M, Carrier M, Renzi M, Pagani F, Modi B, Raspa M, Scavizzi F, Gross CT, Marinelli S, Tremblay M, Caprioli D, Maggi L, Limatola C, Di Angelantonio S, Ragozzino D. 2022. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 70(1), 173–195.","chicago":"Basilico, Bernadette, Laura Ferrucci, Patrizia Ratano, Maria T. Golia, Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” <i>Glia</i>. Wiley, 2022. <a href=\"https://doi.org/10.1002/glia.24101\">https://doi.org/10.1002/glia.24101</a>.","apa":"Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito, M., … Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult mouse hippocampus. <i>Glia</i>. Wiley. <a href=\"https://doi.org/10.1002/glia.24101\">https://doi.org/10.1002/glia.24101</a>","mla":"Basilico, Bernadette, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” <i>Glia</i>, vol. 70, no. 1, Wiley, 2022, pp. 173–95, doi:<a href=\"https://doi.org/10.1002/glia.24101\">10.1002/glia.24101</a>.","short":"B. Basilico, L. Ferrucci, P. Ratano, M.T. Golia, A. Grimaldi, M. Rosito, V. Ferretti, I. Reverte, C. Sanchini, M.C. Marrone, M. Giubettini, V. De Turris, D. Salerno, S. Garofalo, M. St‐Pierre, M. Carrier, M. Renzi, F. Pagani, B. Modi, M. Raspa, F. Scavizzi, C.T. Gross, S. Marinelli, M. Tremblay, D. Caprioli, L. Maggi, C. Limatola, S. Di Angelantonio, D. Ragozzino, Glia 70 (2022) 173–195.","ama":"Basilico B, Ferrucci L, Ratano P, et al. Microglia control glutamatergic synapses in the adult mouse hippocampus. <i>Glia</i>. 2022;70(1):173-195. doi:<a href=\"https://doi.org/10.1002/glia.24101\">10.1002/glia.24101</a>"},"status":"public","isi":1,"month":"01","volume":70,"abstract":[{"lang":"eng","text":"Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses."}],"article_processing_charge":"No","department":[{"_id":"GaNo"}],"issue":"1","acknowledgement":"The work was supported by a grant from MIUR (PRIN 2017HPTFFC_003) to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University, Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza University, Rome and by the Italian Institute of Technology, Rome. The authors thank Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani for help with animal husbandry and transgenic colonies management. They also wish to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism. PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley, CA). Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement.","intvolume":"        70","year":"2022","title":"Microglia control glutamatergic synapses in the adult mouse hippocampus","pmid":1,"publication_identifier":{"eissn":["1098-1136"],"issn":["0894-1491"]},"doi":"10.1002/glia.24101","publication":"Glia","date_published":"2022-01-01T00:00:00Z","language":[{"iso":"eng"}],"scopus_import":"1","type":"journal_article","file_date_updated":"2022-03-04T08:55:27Z","oa":1,"has_accepted_license":"1","ddc":["570"],"author":[{"last_name":"Basilico","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"first_name":"Laura","last_name":"Ferrucci","full_name":"Ferrucci, Laura"},{"last_name":"Ratano","full_name":"Ratano, Patrizia","first_name":"Patrizia"},{"last_name":"Golia","full_name":"Golia, Maria T.","first_name":"Maria T."},{"first_name":"Alfonso","last_name":"Grimaldi","full_name":"Grimaldi, Alfonso"},{"full_name":"Rosito, Maria","last_name":"Rosito","first_name":"Maria"},{"first_name":"Valentina","last_name":"Ferretti","full_name":"Ferretti, Valentina"},{"full_name":"Reverte, Ingrid","last_name":"Reverte","first_name":"Ingrid"},{"last_name":"Sanchini","full_name":"Sanchini, Caterina","first_name":"Caterina"},{"first_name":"Maria C.","last_name":"Marrone","full_name":"Marrone, Maria C."},{"full_name":"Giubettini, Maria","last_name":"Giubettini","first_name":"Maria"},{"last_name":"De Turris","full_name":"De Turris, Valeria","first_name":"Valeria"},{"first_name":"Debora","last_name":"Salerno","full_name":"Salerno, Debora"},{"full_name":"Garofalo, Stefano","last_name":"Garofalo","first_name":"Stefano"},{"first_name":"Marie‐Kim","last_name":"St‐Pierre","full_name":"St‐Pierre, Marie‐Kim"},{"first_name":"Micael","last_name":"Carrier","full_name":"Carrier, Micael"},{"full_name":"Renzi, Massimiliano","last_name":"Renzi","first_name":"Massimiliano"},{"full_name":"Pagani, Francesca","last_name":"Pagani","first_name":"Francesca"},{"first_name":"Brijesh","last_name":"Modi","full_name":"Modi, Brijesh"},{"first_name":"Marcello","full_name":"Raspa, Marcello","last_name":"Raspa"},{"first_name":"Ferdinando","full_name":"Scavizzi, Ferdinando","last_name":"Scavizzi"},{"full_name":"Gross, Cornelius T.","last_name":"Gross","first_name":"Cornelius T."},{"last_name":"Marinelli","full_name":"Marinelli, Silvia","first_name":"Silvia"},{"first_name":"Marie‐Ève","full_name":"Tremblay, Marie‐Ève","last_name":"Tremblay"},{"full_name":"Caprioli, Daniele","last_name":"Caprioli","first_name":"Daniele"},{"full_name":"Maggi, Laura","last_name":"Maggi","first_name":"Laura"},{"first_name":"Cristina","last_name":"Limatola","full_name":"Limatola, Cristina"},{"first_name":"Silvia","full_name":"Di Angelantonio, Silvia","last_name":"Di Angelantonio"},{"last_name":"Ragozzino","full_name":"Ragozzino, Davide","first_name":"Davide"}],"_id":"10818","publisher":"Wiley","publication_status":"published","quality_controlled":"1","corr_author":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","day":"01","external_id":{"isi":["000708025800001"],"pmid":["34661306"]},"keyword":["Cellular and Molecular Neuroscience","Neurology"],"date_updated":"2024-10-09T21:04:02Z","page":"173-195"},{"article_processing_charge":"No","abstract":[{"lang":"eng","text":"Microglia are dynamic cells, constantly surveying their surroundings and interacting with neurons and synapses. Indeed, a wealth of knowledge has revealed a critical role of microglia in modulating synaptic transmission and plasticity in the developing brain. In the past decade, novel pharmacological and genetic strategies have allowed the acute removal of microglia, opening the possibility to explore and understand the role of microglia also in the adult brain. In this review, we summarized and discussed the contribution of microglia depletion strategies to the current understanding of the role of microglia on synaptic function, learning and memory, and behavior both in physiological and pathological conditions. We first described the available microglia depletion methods highlighting their main strengths and weaknesses. We then reviewed the impact of microglia depletion on structural and functional synaptic plasticity. Next, we focused our analysis on the effects of microglia depletion on behavior, including general locomotor activity, sensory perception, motor function, sociability, learning and memory both in healthy animals and animal models of disease. Finally, we integrated the findings from the reviewed studies and discussed the emerging roles of microglia on the maintenance of synaptic function, learning, memory strength and forgetfulness, and the implications of microglia depletion in models of brain disease."}],"month":"11","isi":1,"volume":16,"department":[{"_id":"GaNo"}],"status":"public","oa_version":"Published Version","file":[{"access_level":"open_access","date_created":"2023-01-24T09:16:29Z","creator":"dernst","relation":"main_file","file_id":"12352","success":1,"checksum":"84696213ecf99182c58a9f34b9ff2e23","content_type":"application/pdf","file_size":6399987,"file_name":"2022_FrontiersNeuroscience_Basilico.pdf","date_updated":"2023-01-24T09:16:29Z"}],"citation":{"ama":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. <i>Frontiers in Cellular Neuroscience</i>. 2022;16. doi:<a href=\"https://doi.org/10.3389/fncel.2022.1022431\">10.3389/fncel.2022.1022431</a>","short":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, I. Reverte, Frontiers in Cellular Neuroscience 16 (2022).","apa":"Basilico, B., Ferrucci, L., Khan, A., Di Angelantonio, S., Ragozzino, D., &#38; Reverte, I. (2022). What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. <i>Frontiers in Cellular Neuroscience</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fncel.2022.1022431\">https://doi.org/10.3389/fncel.2022.1022431</a>","mla":"Basilico, Bernadette, et al. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” <i>Frontiers in Cellular Neuroscience</i>, vol. 16, 1022431, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fncel.2022.1022431\">10.3389/fncel.2022.1022431</a>.","chicago":"Basilico, Bernadette, Laura Ferrucci, Azka Khan, Silvia Di Angelantonio, Davide Ragozzino, and Ingrid Reverte. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” <i>Frontiers in Cellular Neuroscience</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fncel.2022.1022431\">https://doi.org/10.3389/fncel.2022.1022431</a>.","ieee":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, and I. Reverte, “What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior,” <i>Frontiers in Cellular Neuroscience</i>, vol. 16. Frontiers Media, 2022.","ista":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. 2022. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. 16, 1022431."},"date_created":"2023-01-12T12:04:50Z","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","date_published":"2022-11-04T00:00:00Z","language":[{"iso":"eng"}],"publication":"Frontiers in Cellular Neuroscience","type":"journal_article","doi":"10.3389/fncel.2022.1022431","title":"What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior","publication_identifier":{"issn":["1662-5102"]},"article_number":"1022431","pmid":1,"acknowledgement":"The write-up of the review was supported by Sapienza University of Rome (Fondi di Ateneo, grant numbers #MA32117A7B698029 and #PH12017270934C3C to SD), Regione Lazio (POR FSE 2014/20, grant number #19036AP000000019 to SD), Fulbright 2019 (grant number\r\n#FSP-P005556 to SD), Institute Pasteur Italia (Fondi Cenci Bolognetti #363 to DR), and Network of European Funding for Neuroscience Research (ERA-NET NEURON Transnational\r\nResearch Projects on Neurodevelopmental Disorders 2021, grant acronym #JTC2021-SHANKAstro to DR).","year":"2022","intvolume":"        16","quality_controlled":"1","publication_status":"published","author":[{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette"},{"first_name":"Laura","full_name":"Ferrucci, Laura","last_name":"Ferrucci"},{"first_name":"Azka","last_name":"Khan","full_name":"Khan, Azka"},{"last_name":"Di Angelantonio","full_name":"Di Angelantonio, Silvia","first_name":"Silvia"},{"first_name":"Davide","full_name":"Ragozzino, Davide","last_name":"Ragozzino"},{"first_name":"Ingrid","full_name":"Reverte, Ingrid","last_name":"Reverte"}],"_id":"12140","has_accepted_license":"1","ddc":["570"],"publisher":"Frontiers Media","oa":1,"file_date_updated":"2023-01-24T09:16:29Z","date_updated":"2023-08-04T08:56:10Z","keyword":["Cellular and Molecular Neuroscience"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"pmid":["36406752"],"isi":["000886526600001"]},"day":"04"},{"project":[{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"}],"keyword":["Neurology (clinical)"],"external_id":{"pmid":["35675510"],"isi":["000807770000001"]},"day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","main_file_link":[{"url":"https://doi.org/10.1093/brain/awac145","open_access":"1"}],"page":"2687-2703","date_updated":"2026-06-18T17:24:52Z","publisher":"Oxford University Press","author":[{"full_name":"Guerrini, Renzo","last_name":"Guerrini","first_name":"Renzo"},{"full_name":"Mei, Davide","last_name":"Mei","first_name":"Davide"},{"id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87","first_name":"Margit Katalin","orcid":"0000-0001-9500-8758","last_name":"Szigeti","full_name":"Szigeti, Margit Katalin"},{"first_name":"Sara","full_name":"Pepe, Sara","last_name":"Pepe"},{"full_name":"Koenig, Mary Kay","last_name":"Koenig","first_name":"Mary Kay"},{"last_name":"Von Allmen","full_name":"Von Allmen, Gretchen","first_name":"Gretchen"},{"full_name":"Cho, Megan T","last_name":"Cho","first_name":"Megan T"},{"first_name":"Kimberly","last_name":"McDonald","full_name":"McDonald, Kimberly"},{"first_name":"Janice","last_name":"Baker","full_name":"Baker, Janice"},{"full_name":"Bhambhani, Vikas","last_name":"Bhambhani","first_name":"Vikas"},{"first_name":"Zöe","full_name":"Powis, Zöe","last_name":"Powis"},{"first_name":"Lance","last_name":"Rodan","full_name":"Rodan, Lance"},{"first_name":"Rima","full_name":"Nabbout, Rima","last_name":"Nabbout"},{"full_name":"Barcia, Giulia","last_name":"Barcia","first_name":"Giulia"},{"last_name":"Rosenfeld","full_name":"Rosenfeld, Jill A","first_name":"Jill A"},{"first_name":"Carlos A","last_name":"Bacino","full_name":"Bacino, Carlos A"},{"full_name":"Mignot, Cyril","last_name":"Mignot","first_name":"Cyril"},{"first_name":"Lillian H","full_name":"Power, Lillian H","last_name":"Power"},{"full_name":"Harris, Catharine J","last_name":"Harris","first_name":"Catharine J"},{"full_name":"Marjanovic, Dragan","last_name":"Marjanovic","first_name":"Dragan"},{"first_name":"Rikke S","last_name":"Møller","full_name":"Møller, Rikke S"},{"first_name":"Trine B","last_name":"Hammer","full_name":"Hammer, Trine B"},{"full_name":"Keski Filppula, Riikka","last_name":"Keski Filppula","first_name":"Riikka"},{"full_name":"Vieira, Päivi","last_name":"Vieira","first_name":"Päivi"},{"full_name":"Hildebrandt, Clara","last_name":"Hildebrandt","first_name":"Clara"},{"full_name":"Sacharow, Stephanie","last_name":"Sacharow","first_name":"Stephanie"},{"full_name":"Maragliano, Luca","last_name":"Maragliano","first_name":"Luca"},{"first_name":"Fabio","full_name":"Benfenati, Fabio","last_name":"Benfenati"},{"full_name":"Lachlan, Katherine","last_name":"Lachlan","first_name":"Katherine"},{"first_name":"Andreas","full_name":"Benneche, Andreas","last_name":"Benneche"},{"last_name":"Petit","full_name":"Petit, Florence","first_name":"Florence"},{"full_name":"de Sainte Agathe, Jean Madeleine","last_name":"de Sainte Agathe","first_name":"Jean Madeleine"},{"full_name":"Hallinan, Barbara","last_name":"Hallinan","first_name":"Barbara"},{"last_name":"Si","full_name":"Si, Yue","first_name":"Yue"},{"full_name":"Wentzensen, Ingrid M","last_name":"Wentzensen","first_name":"Ingrid M"},{"first_name":"Fanggeng","last_name":"Zou","full_name":"Zou, Fanggeng"},{"last_name":"Narayanan","full_name":"Narayanan, Vinodh","first_name":"Vinodh"},{"first_name":"Naomichi","full_name":"Matsumoto, Naomichi","last_name":"Matsumoto"},{"first_name":"Alessandra","full_name":"Boncristiano, Alessandra","last_name":"Boncristiano"},{"first_name":"Giancarlo","full_name":"la Marca, Giancarlo","last_name":"la Marca"},{"first_name":"Mitsuhiro","full_name":"Kato, Mitsuhiro","last_name":"Kato"},{"last_name":"Anderson","full_name":"Anderson, Kristin","first_name":"Kristin"},{"first_name":"Carmen","full_name":"Barba, Carmen","last_name":"Barba"},{"full_name":"Sturiale, Luisa","last_name":"Sturiale","first_name":"Luisa"},{"last_name":"Garozzo","full_name":"Garozzo, Domenico","first_name":"Domenico"},{"first_name":"Roberto","full_name":"Bei, Roberto","last_name":"Bei"},{"first_name":"Laura","last_name":"Masuelli","full_name":"Masuelli, Laura"},{"full_name":"Conti, Valerio","last_name":"Conti","first_name":"Valerio"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Fassio","full_name":"Fassio, Anna","first_name":"Anna"}],"_id":"12174","ddc":["570"],"oa":1,"quality_controlled":"1","publication_status":"published","publication_identifier":{"issn":["0006-8950"],"eissn":["1460-2156"]},"pmid":1,"title":"Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis","year":"2022","intvolume":"       145","issue":"8","acknowledgement":"We thank all patients and family members for their participation in this study. We thank Melanie Pieraks and Eva Reinthaler (Neurolentech, Austria) for generating the human iPSC lines and\r\nfor performing quality checks. We thank Vanessa Zheden and Daniel Gütl for their excellent technical support in the specimen preparation for transmission electron microscopy and Flavia Leite for preparing the lentiviruses. The support from Electron Microscopy Facility and Molecular Biology Services at IST Austria is greatly acknowledged. We would like to thank Doctors Jane Hurst and Richard Scott for their help in retrieving the detailed clinical information of Patient 17. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. See Supplementary Material for Undiagnosed Disease Network consortium details. Genetic information on Patient 23 was made available through access to the data and findings generated by the 100 000 Genomes\r\nProject; www.genomicsengland.co.uk (to K.L.). \r\nThis work was supported by the EU 7th Framework Programme (FP7) under the project DESIRE grant N602531 (to R.G.); the Regione Toscana under the Call for Health 2018 (grant\r\nDECODE-EE) (to R.G.); the ‘Brain Project’ by Fondazione Cassa di Risparmio di Firenze (to R.G.); IRCCS Ospedale Policlinico San Martino 5×1000 and Ricerca Corrente (to A.F. and F.B.). The European Reference Network (ERN) for rare and complex epilepsies (EpiCARE) provided financial support for meetings organization. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication\r\nare those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). This study makes use of DECIPHER (https://www.deciphergenomics.org), which is funded by Wellcome. K.K.-S. was supported by the ISTplus fellowship. ","type":"journal_article","scopus_import":"1","date_published":"2022-08-01T00:00:00Z","publication":"Brain","language":[{"iso":"eng"}],"doi":"10.1093/brain/awac145","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"citation":{"mla":"Guerrini, Renzo, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” <i>Brain</i>, vol. 145, no. 8, Oxford University Press, 2022, pp. 2687–703, doi:<a href=\"https://doi.org/10.1093/brain/awac145\">10.1093/brain/awac145</a>.","apa":"Guerrini, R., Mei, D., Szigeti, M. K., Pepe, S., Koenig, M. K., Von Allmen, G., … Fassio, A. (2022). Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. <i>Brain</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/brain/awac145\">https://doi.org/10.1093/brain/awac145</a>","chicago":"Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” <i>Brain</i>. Oxford University Press, 2022. <a href=\"https://doi.org/10.1093/brain/awac145\">https://doi.org/10.1093/brain/awac145</a>.","ista":"Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA, Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB, Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 145(8), 2687–2703.","ieee":"R. Guerrini <i>et al.</i>, “Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis,” <i>Brain</i>, vol. 145, no. 8. Oxford University Press, pp. 2687–2703, 2022.","ama":"Guerrini R, Mei D, Szigeti MK, et al. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. <i>Brain</i>. 2022;145(8):2687-2703. doi:<a href=\"https://doi.org/10.1093/brain/awac145\">10.1093/brain/awac145</a>","short":"R. Guerrini, D. Mei, M.K. Szigeti, S. Pepe, M.K. Koenig, G. Von Allmen, M.T. Cho, K. McDonald, J. Baker, V. Bhambhani, Z. Powis, L. Rodan, R. Nabbout, G. Barcia, J.A. Rosenfeld, C.A. Bacino, C. Mignot, L.H. Power, C.J. Harris, D. Marjanovic, R.S. Møller, T.B. Hammer, R. Keski Filppula, P. Vieira, C. Hildebrandt, S. Sacharow, L. Maragliano, F. Benfenati, K. Lachlan, A. Benneche, F. Petit, J.M. de Sainte Agathe, B. Hallinan, Y. Si, I.M. Wentzensen, F. Zou, V. Narayanan, N. Matsumoto, A. Boncristiano, G. la Marca, M. Kato, K. Anderson, C. Barba, L. Sturiale, D. Garozzo, R. Bei, L. Masuelli, V. Conti, G. Novarino, A. Fassio, Brain 145 (2022) 2687–2703."},"oa_version":"Published Version","article_type":"original","ec_funded":1,"date_created":"2023-01-12T12:11:45Z","department":[{"_id":"GaNo"}],"article_processing_charge":"No","month":"08","isi":1,"volume":145,"abstract":[{"lang":"eng","text":"Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.\r\nHere we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.</jats:p>\r\n               <jats:p>Fibroblasts of two patients with developmental epileptic encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased organelle pH, consistent with lysosomal impairment and loss of V-ATPase function. Fibroblasts of two patients with milder disease, exhibited a different phenotype with increased Lysotracker staining, decreased organelle pH and no significant modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes in cellular extracts from four patients revealed discrete accumulation. Transmission electron microscopy of fibroblasts of four patients with variable severity and of induced pluripotent stem cell-derived neurons from two patients with developmental epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic material and lamellated membrane structures resembling phospholipids. Quantitative assessment in induced pluripotent stem cell-derived neurons identified significantly smaller lysosomes.\r\nATP6V1A-related encephalopathy represents a new paradigm among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane protein causing altered pH homeostasis. Its pathophysiology implies intracellular accumulation of substrates whose composition remains unclear, and a combination of developmental brain abnormalities and neurodegenerative changes established during prenatal and early postanal development, whose severity is variably determined by specific pathogenic variants."}],"status":"public"},{"quality_controlled":"1","publication_status":"published","publisher":"Frontiers Media","ddc":["570"],"has_accepted_license":"1","_id":"12268","author":[{"orcid":"0000-0003-1843-3173","last_name":"Basilico","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette"},{"full_name":"Palamà, Ilaria Elena","last_name":"Palamà","first_name":"Ilaria Elena"},{"first_name":"Stefania","full_name":"D’Amone, Stefania","last_name":"D’Amone"},{"full_name":"Lauro, Clotilde","last_name":"Lauro","first_name":"Clotilde"},{"full_name":"Rosito, Maria","last_name":"Rosito","first_name":"Maria"},{"first_name":"Maddalena","full_name":"Grieco, Maddalena","last_name":"Grieco"},{"last_name":"Ratano","full_name":"Ratano, Patrizia","first_name":"Patrizia"},{"full_name":"Cordella, Federica","last_name":"Cordella","first_name":"Federica"},{"first_name":"Caterina","last_name":"Sanchini","full_name":"Sanchini, Caterina"},{"first_name":"Silvia","full_name":"Di Angelantonio, Silvia","last_name":"Di Angelantonio"},{"first_name":"Davide","full_name":"Ragozzino, Davide","last_name":"Ragozzino"},{"first_name":"Mariafrancesca","full_name":"Cascione, Mariafrancesca","last_name":"Cascione"},{"full_name":"Gigli, Giuseppe","last_name":"Gigli","first_name":"Giuseppe"},{"full_name":"Cortese, Barbara","last_name":"Cortese","first_name":"Barbara"}],"file_date_updated":"2023-01-30T10:25:21Z","oa":1,"date_updated":"2023-08-04T09:54:16Z","keyword":["Cancer Research","Oncology"],"external_id":{"isi":["000856524900001"],"pmid":["36091138"]},"day":"25","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"GaNo"}],"abstract":[{"text":"The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment.","lang":"eng"}],"isi":1,"volume":12,"month":"08","article_processing_charge":"No","status":"public","citation":{"ama":"Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. <i>Frontiers in Oncology</i>. 2022;12. doi:<a href=\"https://doi.org/10.3389/fonc.2022.983507\">10.3389/fonc.2022.983507</a>","short":"B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P. Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione, G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022).","ieee":"B. Basilico <i>et al.</i>, “Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells,” <i>Frontiers in Oncology</i>, vol. 12. Frontiers Media, 2022.","ista":"Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B. 2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507.","mla":"Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” <i>Frontiers in Oncology</i>, vol. 12, 983507, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fonc.2022.983507\">10.3389/fonc.2022.983507</a>.","apa":"Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M., … Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. <i>Frontiers in Oncology</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fonc.2022.983507\">https://doi.org/10.3389/fonc.2022.983507</a>","chicago":"Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro, Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” <i>Frontiers in Oncology</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fonc.2022.983507\">https://doi.org/10.3389/fonc.2022.983507</a>."},"file":[{"access_level":"open_access","file_id":"12450","relation":"main_file","date_created":"2023-01-30T10:25:21Z","creator":"dernst","checksum":"efc7edf9f626af31853790c5b598a68c","success":1,"file_name":"2022_FrontiersOntology_Basilico.pdf","date_updated":"2023-01-30T10:25:21Z","file_size":13588502,"content_type":"application/pdf"}],"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_created":"2023-01-16T10:00:28Z","article_type":"original","type":"journal_article","publication":"Frontiers in Oncology","language":[{"iso":"eng"}],"date_published":"2022-08-25T00:00:00Z","scopus_import":"1","doi":"10.3389/fonc.2022.983507","article_number":"983507","pmid":1,"publication_identifier":{"issn":["2234-943X"]},"title":"Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells","intvolume":"        12","year":"2022","acknowledgement":"The research leading to these results has received funding from AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG 2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia: DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela Marchetti for practical administrative support."},{"oa_version":"None","_id":"17075","author":[{"first_name":"Manuel","full_name":"Palacín, Manuel","last_name":"Palacín"},{"first_name":"Stefan","last_name":"Bröer","full_name":"Bröer, Stefan"},{"orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"publisher":"Springer Nature","citation":{"ama":"Palacín M, Bröer S, Novarino G. Amino Acid Transport Defects. In: Blau N, Vici CD, Ferreira CR, Vianey-Saban C, van Karnebeek CDM, eds. <i>Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases</i>. 2nd ed. Cham: Springer Nature; 2022:291-312. doi:<a href=\"https://doi.org/10.1007/978-3-030-67727-5_18\">10.1007/978-3-030-67727-5_18</a>","short":"M. Palacín, S. Bröer, G. Novarino, in:, N. Blau, C.D. Vici, C.R. Ferreira, C. Vianey-Saban, C.D.M. van Karnebeek (Eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, 2nd ed., Springer Nature, Cham, 2022, pp. 291–312.","ista":"Palacín M, Bröer S, Novarino G. 2022.Amino Acid Transport Defects. In: Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. , 291–312.","ieee":"M. Palacín, S. Bröer, and G. Novarino, “Amino Acid Transport Defects,” in <i>Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases</i>, 2nd ed., N. Blau, C. D. Vici, C. R. Ferreira, C. Vianey-Saban, and C. D. M. van Karnebeek, Eds. Cham: Springer Nature, 2022, pp. 291–312.","apa":"Palacín, M., Bröer, S., &#38; Novarino, G. (2022). Amino Acid Transport Defects. In N. Blau, C. D. Vici, C. R. Ferreira, C. Vianey-Saban, &#38; C. D. M. van Karnebeek (Eds.), <i>Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases</i> (2nd ed., pp. 291–312). Cham: Springer Nature. <a href=\"https://doi.org/10.1007/978-3-030-67727-5_18\">https://doi.org/10.1007/978-3-030-67727-5_18</a>","mla":"Palacín, Manuel, et al. “Amino Acid Transport Defects.” <i>Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases</i>, edited by Nenad Blau et al., 2nd ed., Springer Nature, 2022, pp. 291–312, doi:<a href=\"https://doi.org/10.1007/978-3-030-67727-5_18\">10.1007/978-3-030-67727-5_18</a>.","chicago":"Palacín, Manuel, Stefan Bröer, and Gaia Novarino. “Amino Acid Transport Defects.” In <i>Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases</i>, edited by Nenad Blau, Carlo Dionisi Vici, Carlos R.  Ferreira, Christine Vianey-Saban, and Clara D.M. van Karnebeek, 2nd ed., 291–312. Cham: Springer Nature, 2022. <a href=\"https://doi.org/10.1007/978-3-030-67727-5_18\">https://doi.org/10.1007/978-3-030-67727-5_18</a>."},"date_created":"2024-05-29T06:13:04Z","article_processing_charge":"No","month":"02","abstract":[{"text":"Disorders associated with the malfunction of amino acid transporters mainly affect the function of the intestine, kidney, brain, and liver. Mutations of brain amino acid transporters, for example, alter neuronal excitability (e.g., episodic ataxia due to SLC1A3 (EAAT1) defect and hyperekplexia due to SLC6A5 (GLYT2) deficiency) or brain development (SLC1A1 (EAAT3), SLC3A2/SLC7A5 (CD98hc/LAT1), and SLC1A4 (ASCT1) deficiencies). Mutations of renal and intestinal amino acid transporters SLC3A1/SLC7A9 (rBAT/b0,+AT) and SLC1A1 (EAAT3) cause renal problems (cystinuria and dicarboxylic aminoaciduria, respectively) and malabsorption that can affect whole-body homoeostasis (Hartnup disorder SLC6A19 (B0AT1), lysinuric protein intolerance SLC3A2/SLC7A7 (CD98hc/y+LAT1), and hyperdibasic aminoaciduria type 1). Mutations in the neuronal system A amino acid transporter SLC38A8 (SNAT8) cause eye developmental and visual defects. Inborn errors associated with mitochondrial SLC25 family members such as SLC25A12 (neuronal- and muscle-specific mitochondrial aspartate/glutamate transporter 1; AGC1) (global cerebral hypomyelination), SLC25A13 (aspartate/glutamate transporter 2) (citrin deficiency), SLC25A15 (ornithine-citrulline carrier 2) (homocitrullinuria, hyperornithinemia, and hyperammonemia syndrome), and SLC25A22 (mitochondrial glutamate/H+ symporter 1, GC1) (neonatal myoclonic epilepsy) will be dealt within Chap. 43 (defects of mitochondrial carriers).","lang":"eng"}],"department":[{"_id":"GaNo"}],"quality_controlled":"1","status":"public","publication_status":"published","title":"Amino Acid Transport Defects","publication_identifier":{"eisbn":["9783030677275"],"isbn":["9783030677268"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","place":"Cham","acknowledgement":"The authors thank Dr. Christian Lueck (Canberra Hospital) for clarification of differential diagnosis in cases of episodic ataxia. The authors thank Dr. Rafael Artuch (Hospital San Joan de Deu, Barcelona) for reference values of plasma amino acid concentration. The authors also thank Lisa Kraus (Institute of Science and Technology-Austria) and Dr. Susanna Bodoy (IRB-Barcelona) that helped in preparing tables and bibliography.","day":"22","year":"2022","edition":"2","scopus_import":"1","publication":"Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases","date_published":"2022-02-22T00:00:00Z","language":[{"iso":"eng"}],"type":"book_chapter","doi":"10.1007/978-3-030-67727-5_18","date_updated":"2024-07-31T11:45:50Z","editor":[{"full_name":"Blau, Nenad","last_name":"Blau","first_name":"Nenad"},{"first_name":"Carlo Dionisi","last_name":"Vici","full_name":"Vici, Carlo Dionisi"},{"last_name":"Ferreira","full_name":"Ferreira, Carlos R. ","first_name":"Carlos R. "},{"last_name":"Vianey-Saban","full_name":"Vianey-Saban, Christine","first_name":"Christine"},{"last_name":"van Karnebeek","full_name":"van Karnebeek, Clara D.M.","first_name":"Clara D.M."}],"page":"291-312"},{"date_updated":"2026-06-26T22:30:30Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","external_id":{"isi":["000785983900003"],"pmid":["35385734"]},"day":"05","project":[{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF"}],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"publication_status":"published","quality_controlled":"1","corr_author":"1","oa":1,"file_date_updated":"2022-04-15T09:06:25Z","ddc":["570"],"has_accepted_license":"1","author":[{"last_name":"Villa","full_name":"Villa, Carlo Emanuele","first_name":"Carlo Emanuele"},{"first_name":"Cristina","full_name":"Cheroni, Cristina","last_name":"Cheroni"},{"first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","last_name":"Dotter","full_name":"Dotter, Christoph"},{"first_name":"Alejandro","last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro"},{"first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","last_name":"Oliveira","full_name":"Oliveira, Bárbara"},{"full_name":"Sacco, Roberto","last_name":"Sacco","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto"},{"id":"365A65F8-F248-11E8-B48F-1D18A9856A87","first_name":"Aysan Çerağ","last_name":"Yahya","full_name":"Yahya, Aysan Çerağ"},{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","full_name":"Morandell, Jasmin"},{"first_name":"Michele","last_name":"Gabriele","full_name":"Gabriele, Michele"},{"full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli","orcid":"0000-0002-7667-6854","first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"full_name":"Gabitto, Mariano","last_name":"Gabitto","first_name":"Mariano"},{"orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Giuseppe","full_name":"Testa, Giuseppe","last_name":"Testa"},{"full_name":"Novarino, Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"_id":"11160","publisher":"Elsevier","doi":"10.1016/j.celrep.2022.110615","date_published":"2022-04-05T00:00:00Z","language":[{"iso":"eng"}],"publication":"Cell Reports","scopus_import":"1","type":"journal_article","acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","issue":"1","intvolume":"        39","year":"2022","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","publication_identifier":{"issn":["2211-1247"]},"pmid":1,"article_number":"110615","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"18681"},{"relation":"dissertation_contains","id":"18674","status":"public"},{"id":"12364","status":"public","relation":"dissertation_contains"}]},"status":"public","volume":39,"isi":1,"month":"04","abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"article_processing_charge":"Yes","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"article_type":"original","date_created":"2022-04-15T09:03:10Z","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file":[{"success":1,"checksum":"b4e8d68f0268dec499af333e6fd5d8e1","content_type":"application/pdf","file_size":"7808644","date_updated":"2022-04-15T09:06:25Z","file_name":"2022_CellReports_Villa.pdf","access_level":"open_access","creator":"dernst","date_created":"2022-04-15T09:06:25Z","relation":"main_file","file_id":"11164"}],"oa_version":"Published Version","citation":{"ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}]},{"publication_status":"published","corr_author":"1","file_date_updated":"2023-09-20T22:30:03Z","oa":1,"has_accepted_license":"1","ddc":["570"],"author":[{"full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"}],"_id":"12364","publisher":"Institute of Science and Technology Austria","date_updated":"2026-04-07T14:30:57Z","page":"152","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","day":"19","project":[{"grant_number":"401299","name":"Probing development and reversibility of autism spectrum disorders","_id":"254BA948-B435-11E9-9278-68D0E5697425"},{"_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","grant_number":"707964"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","grant_number":"I04205","call_identifier":"FWF"}],"related_material":{"record":[{"status":"public","id":"11160","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","id":"3","status":"public"}]},"status":"public","month":"09","abstract":[{"text":"Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders character\u0002ized by behavioral symptoms such as problems in social communication and interaction, as\r\nwell as repetitive, restricted behaviors and interests. These disorders show a high degree\r\nof heritability and hundreds of risk genes have been identifed using high throughput\r\nsequencing technologies. This genetic heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD but at the same time given rise to the concept of convergent\r\nmechanisms. Previous studies have identifed that risk genes for ASD broadly converge\r\nonto specifc functional categories with transcriptional regulation being one of the biggest\r\ngroups. In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe link the regulatory function of Setd5 to its interaction with the Paf1 and the NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing. While the former\r\nwere generated earlier in CHD8+/- organoids, the generation of the latter was shifted to\r\nlater times in favor of a prolonged progenitor expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B, KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral ganglionic eminence. As this project is still ongoing at the time of writing, future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying this shift with\r\nthe aim of linking these three ASD risk genes through biological convergence.","lang":"eng"}],"article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"ec_funded":1,"date_created":"2023-01-24T13:09:57Z","file":[{"relation":"main_file","creator":"cchlebak","date_created":"2023-01-24T13:15:45Z","file_id":"12365","access_level":"open_access","date_updated":"2023-09-20T22:30:03Z","file_size":20457465,"file_name":"220923_Thesis_CDotter_Final.pdf","content_type":"application/pdf","embargo":"2023-09-19","checksum":"896f4cac9adb6d3f26a6605772f4e1a3"},{"content_type":"application/x-zip-compressed","file_size":22433512,"date_updated":"2023-09-20T22:30:03Z","file_name":"latex_source_CDotter_Thesis_2022.zip","checksum":"ad01bb20da163be6893b7af832e58419","date_created":"2023-02-02T09:15:35Z","creator":"cchlebak","relation":"source_file","file_id":"12482","embargo_to":"open_access","access_level":"closed"}],"oa_version":"Published Version","citation":{"ama":"Dotter C. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12094\">10.15479/at:ista:12094</a>","short":"C. Dotter, Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.","mla":"Dotter, Christoph. <i>Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12094\">10.15479/at:ista:12094</a>.","apa":"Dotter, C. (2022). <i>Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12094\">https://doi.org/10.15479/at:ista:12094</a>","chicago":"Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12094\">https://doi.org/10.15479/at:ista:12094</a>.","ista":"Dotter C. 2022. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria.","ieee":"C. Dotter, “Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022."},"OA_place":"publisher","alternative_title":["ISTA Thesis"],"doi":"10.15479/at:ista:12094","date_published":"2022-09-19T00:00:00Z","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"type":"dissertation","year":"2022","title":"Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder","publication_identifier":{"issn":["2663-337X"]}},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"09","year":"2022","title":"Saturated reconstruction of living brain tissue","doi":"10.1101/2022.03.16.484431","date_updated":"2026-06-26T22:30:45Z","publication":"bioRxiv","date_published":"2022-05-09T00:00:00Z","language":[{"iso":"eng"}],"type":"preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.03.16.484431"}],"date_created":"2022-08-23T11:07:59Z","oa":1,"_id":"11943","author":[{"first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp"},{"full_name":"Miguel Villalba, Eder","last_name":"Miguel Villalba","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder"},{"orcid":"0000-0003-3862-1235","last_name":"Michalska","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"full_name":"Wei, Donglai","last_name":"Wei","first_name":"Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"full_name":"Watson, Jake","last_name":"Watson","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"first_name":"Jakob","last_name":"Troidl","full_name":"Troidl, Jakob"},{"last_name":"Beyer","full_name":"Beyer, Johanna","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","last_name":"Ben Simon","full_name":"Ben Simon, Yoav"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","last_name":"Jahr","orcid":"0000-0003-0201-2315","full_name":"Jahr, Wiebke"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"first_name":"Johannes","full_name":"Broichhagen, Johannes","last_name":"Broichhagen"},{"full_name":"Grant, Seth G. N.","last_name":"Grant","first_name":"Seth G. N."},{"full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385","last_name":"Bickel","first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"Preprint","OA_place":"repository","publisher":"Cold Spring Harbor Laboratory","citation":{"chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>"},"related_material":{"record":[{"relation":"later_version","id":"13267","status":"public"},{"status":"public","id":"12470","relation":"dissertation_contains"}]},"publication_status":"draft","status":"public","article_processing_charge":"No","abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"month":"05","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"corr_author":"1"},{"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2022","day":"18","publication":"bioRxiv","date_published":"2022-08-18T00:00:00Z","language":[{"iso":"eng"}],"type":"preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}],"doi":"10.1101/2022.08.17.504272","date_updated":"2026-06-26T22:30:45Z","_id":"11950","oa_version":"Preprint","author":[{"first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","full_name":"Velicky, Philipp","last_name":"Velicky","orcid":"0000-0002-2340-7431"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"last_name":"Siegert","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Cold Spring Harbor Laboratory","citation":{"ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>."},"date_created":"2022-08-24T08:24:52Z","oa":1,"article_processing_charge":"No","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons."}],"month":"08","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"corr_author":"1","related_material":{"record":[{"id":"12470","status":"public","relation":"dissertation_contains"}]},"status":"public","publication_status":"draft"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_created":"2024-04-03T08:02:52Z","article_type":"original","citation":{"chicago":"Cordella, Federica, Caterina Sanchini, Maria Rosito, Laura Ferrucci, Natalia Pediconi, Barbara Cortese, Francesca Guerrieri, et al. “Antibiotics Treatment Modulates Microglia–Synapses Interaction.” <i>Cells</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/cells10102648\">https://doi.org/10.3390/cells10102648</a>.","apa":"Cordella, F., Sanchini, C., Rosito, M., Ferrucci, L., Pediconi, N., Cortese, B., … Di Angelantonio, S. (2021). Antibiotics treatment modulates microglia–synapses interaction. <i>Cells</i>. MDPI. <a href=\"https://doi.org/10.3390/cells10102648\">https://doi.org/10.3390/cells10102648</a>","mla":"Cordella, Federica, et al. “Antibiotics Treatment Modulates Microglia–Synapses Interaction.” <i>Cells</i>, vol. 10, no. 10, 2648, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/cells10102648\">10.3390/cells10102648</a>.","ista":"Cordella F, Sanchini C, Rosito M, Ferrucci L, Pediconi N, Cortese B, Guerrieri F, Pascucci GR, Antonangeli F, Peruzzi G, Giubettini M, Basilico B, Pagani F, Grimaldi A, D’Alessandro G, Limatola C, Ragozzino D, Di Angelantonio S. 2021. Antibiotics treatment modulates microglia–synapses interaction. Cells. 10(10), 2648.","ieee":"F. Cordella <i>et al.</i>, “Antibiotics treatment modulates microglia–synapses interaction,” <i>Cells</i>, vol. 10, no. 10. MDPI, 2021.","short":"F. Cordella, C. Sanchini, M. Rosito, L. Ferrucci, N. Pediconi, B. Cortese, F. Guerrieri, G.R. Pascucci, F. Antonangeli, G. Peruzzi, M. Giubettini, B. Basilico, F. Pagani, A. Grimaldi, G. D’Alessandro, C. Limatola, D. Ragozzino, S. Di Angelantonio, Cells 10 (2021).","ama":"Cordella F, Sanchini C, Rosito M, et al. Antibiotics treatment modulates microglia–synapses interaction. <i>Cells</i>. 2021;10(10). doi:<a href=\"https://doi.org/10.3390/cells10102648\">10.3390/cells10102648</a>"},"oa_version":"Published Version","file":[{"access_level":"open_access","file_id":"15303","date_created":"2024-04-09T08:51:22Z","creator":"dernst","relation":"main_file","checksum":"1a3b251ce82e2b9474b852d2abe5bb03","success":1,"content_type":"application/pdf","date_updated":"2024-04-09T08:51:22Z","file_size":2196672,"file_name":"2021_Cells_Cordella.pdf"}],"status":"public","department":[{"_id":"GaNo"}],"article_processing_charge":"Yes","month":"10","abstract":[{"text":"‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain function and behavior. Moreover, gut microbiota composition constantly controls microglia maturation, as revealed by morphological observations and gene expression analysis. However, it is unclear whether microglia functional properties and crosstalk with neurons, known to shape and modulate synaptic development and function, are influenced by the gut microbiota. Here, we investigated how antibiotic-mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. Antibiotics treatment was unable to modulate synaptic function in CX3CR1-deficient mice, pointing to an involvement of microglia–neuron crosstalk through the CX3CL1/CX3CR1 axis in the effect of dysbiosis on neuronal functions. Together, our findings show that antibiotic alteration of gut microbiota impairs synaptic efficacy, suggesting that CX3CL1/CX3CR1 signaling supporting microglia is a major player in in the gut–brain axis, and in particular in the gut microbiota-to-neuron communication pathway.","lang":"eng"}],"volume":10,"year":"2021","intvolume":"        10","issue":"10","pmid":1,"article_number":"2648","publication_identifier":{"issn":["2073-4409"]},"title":"Antibiotics treatment modulates microglia–synapses interaction","doi":"10.3390/cells10102648","type":"journal_article","language":[{"iso":"eng"}],"date_published":"2021-10-04T00:00:00Z","publication":"Cells","file_date_updated":"2024-04-09T08:51:22Z","oa":1,"publisher":"MDPI","_id":"15278","author":[{"first_name":"Federica","full_name":"Cordella, Federica","last_name":"Cordella"},{"first_name":"Caterina","full_name":"Sanchini, Caterina","last_name":"Sanchini"},{"last_name":"Rosito","full_name":"Rosito, Maria","first_name":"Maria"},{"first_name":"Laura","full_name":"Ferrucci, Laura","last_name":"Ferrucci"},{"last_name":"Pediconi","full_name":"Pediconi, Natalia","first_name":"Natalia"},{"first_name":"Barbara","last_name":"Cortese","full_name":"Cortese, Barbara"},{"first_name":"Francesca","last_name":"Guerrieri","full_name":"Guerrieri, Francesca"},{"last_name":"Pascucci","full_name":"Pascucci, Giuseppe Rubens","first_name":"Giuseppe Rubens"},{"first_name":"Fabrizio","full_name":"Antonangeli, Fabrizio","last_name":"Antonangeli"},{"full_name":"Peruzzi, Giovanna","last_name":"Peruzzi","first_name":"Giovanna"},{"last_name":"Giubettini","full_name":"Giubettini, Maria","first_name":"Maria"},{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette","full_name":"Basilico, Bernadette","last_name":"Basilico","orcid":"0000-0003-1843-3173"},{"last_name":"Pagani","full_name":"Pagani, Francesca","first_name":"Francesca"},{"full_name":"Grimaldi, Alfonso","last_name":"Grimaldi","first_name":"Alfonso"},{"last_name":"D’Alessandro","full_name":"D’Alessandro, Giuseppina","first_name":"Giuseppina"},{"full_name":"Limatola, Cristina","last_name":"Limatola","first_name":"Cristina"},{"last_name":"Ragozzino","full_name":"Ragozzino, Davide","first_name":"Davide"},{"first_name":"Silvia","full_name":"Di Angelantonio, Silvia","last_name":"Di Angelantonio"}],"has_accepted_license":"1","ddc":["610"],"publication_status":"published","quality_controlled":"1","day":"04","external_id":{"pmid":["34685628"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["General Medicine"],"date_updated":"2024-04-09T08:53:23Z"},{"project":[{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF"}],"external_id":{"isi":["000834044200002"]},"day":"30","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2025-04-15T07:29:28Z","publisher":"MDPI","_id":"10281","author":[{"full_name":"Vasic, Verica","last_name":"Vasic","first_name":"Verica"},{"first_name":"Mattson S.O.","full_name":"Jones, Mattson S.O.","last_name":"Jones"},{"full_name":"Haslinger, Denise","last_name":"Haslinger","id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","first_name":"Denise"},{"last_name":"Knaus","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa"},{"first_name":"Michael J.","full_name":"Schmeisser, Michael J.","last_name":"Schmeisser"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Chiocchetti","full_name":"Chiocchetti, Andreas G.","first_name":"Andreas G."}],"ddc":["570"],"has_accepted_license":"1","oa":1,"file_date_updated":"2022-05-16T07:02:27Z","quality_controlled":"1","publication_status":"published","publication_identifier":{"eissn":["2073-4425"]},"article_number":"1746","title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","year":"2021","intvolume":"        12","acknowledgement":"This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811); Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was also supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24) both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes for her support in preparing this manuscript.","issue":"11","type":"journal_article","scopus_import":"1","language":[{"iso":"eng"}],"publication":"Genes","date_published":"2021-10-30T00:00:00Z","doi":"10.3390/genes12111746","alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"citation":{"ista":"Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746.","ieee":"V. Vasic <i>et al.</i>, “Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment,” <i>Genes</i>, vol. 12, no. 11. MDPI, 2021.","apa":"Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino, G., &#38; Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. MDPI. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>","mla":"Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>, vol. 12, no. 11, 1746, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>.","chicago":"Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>.","ama":"Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. 2021;12(11). doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>","short":"V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino, A.G. Chiocchetti, Genes 12 (2021)."},"oa_version":"Published Version","file":[{"success":1,"checksum":"256cb832a9c3051c7dc741f6423b8cbd","content_type":"application/pdf","file_name":"2021_Genes_Vasic.pdf","date_updated":"2022-05-16T07:02:27Z","file_size":1335308,"access_level":"open_access","creator":"dernst","date_created":"2022-05-16T07:02:27Z","relation":"main_file","file_id":"11380"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_created":"2021-11-14T23:01:24Z","article_type":"original","ec_funded":1,"department":[{"_id":"GaNo"}],"article_processing_charge":"No","volume":12,"abstract":[{"lang":"eng","text":"Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems"}],"isi":1,"month":"10","status":"public"},{"publication_identifier":{"issn":["2050-084X"]},"article_number":"e71575","title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","year":"2021","intvolume":"        10","acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","type":"journal_article","scopus_import":"1","publication":"eLife","date_published":"2021-11-17T00:00:00Z","language":[{"iso":"eng"}],"doi":"10.7554/elife.71575","citation":{"ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","ieee":"M. J. Conde-Dusman <i>et al.</i>, “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.71575\">https://doi.org/10.7554/elife.71575</a>","mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” <i>ELife</i>, vol. 10, e71575, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.71575\">10.7554/elife.71575</a>.","chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.71575\">https://doi.org/10.7554/elife.71575</a>.","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.71575\">10.7554/elife.71575</a>","short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021)."},"oa_version":"Published Version","file":[{"file_id":"10302","date_created":"2021-11-18T07:02:02Z","creator":"lgarciar","relation":"main_file","access_level":"open_access","content_type":"application/pdf","date_updated":"2021-11-18T07:02:02Z","file_name":"elife-71575-v1.pdf","file_size":2477302,"checksum":"59318e9e41507cec83c2f4070e6ad540","success":1}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_created":"2021-11-18T06:59:45Z","article_type":"original","department":[{"_id":"GaNo"}],"article_processing_charge":"No","abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"isi":1,"volume":10,"month":"11","status":"public","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"day":"17","external_id":{"isi":["000720945900001"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2024-10-21T06:02:05Z","publisher":"eLife Sciences Publications","_id":"10301","author":[{"full_name":"Conde-Dusman, María J","last_name":"Conde-Dusman","first_name":"María J"},{"last_name":"Dey","full_name":"Dey, Partha N","first_name":"Partha N"},{"first_name":"Óscar","last_name":"Elía-Zudaire","full_name":"Elía-Zudaire, Óscar"},{"last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E","first_name":"Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Carmen","last_name":"García-Lira","full_name":"García-Lira, Carmen"},{"last_name":"Grand","full_name":"Grand, Teddy","first_name":"Teddy"},{"last_name":"Briz","full_name":"Briz, Victor","first_name":"Victor"},{"first_name":"Eric R","full_name":"Velasco, Eric R","last_name":"Velasco"},{"first_name":"Raül","last_name":"Andero Galí","full_name":"Andero Galí, Raül"},{"first_name":"Sergio","full_name":"Niñerola, Sergio","last_name":"Niñerola"},{"first_name":"Angel","full_name":"Barco, Angel","last_name":"Barco"},{"last_name":"Paoletti","full_name":"Paoletti, Pierre","first_name":"Pierre"},{"last_name":"Wesseling","full_name":"Wesseling, John F","first_name":"John F"},{"last_name":"Gardoni","full_name":"Gardoni, Fabrizio","first_name":"Fabrizio"},{"last_name":"Tavalin","full_name":"Tavalin, Steven J","first_name":"Steven J"},{"first_name":"Isabel","last_name":"Perez-Otaño","full_name":"Perez-Otaño, Isabel"}],"ddc":["570"],"has_accepted_license":"1","oa":1,"file_date_updated":"2021-11-18T07:02:02Z","quality_controlled":"1","publication_status":"published"},{"year":"2021","intvolume":"        41","issue":"7","publication_identifier":{"eissn":["1559-7016"],"issn":["0271-678x"]},"pmid":1,"title":"Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib","doi":"10.1177/0271678X20965500","type":"journal_article","scopus_import":"1","language":[{"iso":"eng"}],"date_published":"2021-07-01T00:00:00Z","publication":"Journal of Cerebral Blood Flow and Metabolism","date_created":"2020-11-06T08:39:01Z","article_type":"original","citation":{"mla":"Tournier, N., et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” <i>Journal of Cerebral Blood Flow and Metabolism</i>, vol. 41, no. 7, SAGE Publications, 2021, pp. 1634–46, doi:<a href=\"https://doi.org/10.1177/0271678X20965500\">10.1177/0271678X20965500</a>.","apa":"Tournier, N., Goutal, S., Mairinger, S., Lozano, I., Filip, T., Sauberer, M., … Langer, O. (2021). Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. <i>Journal of Cerebral Blood Flow and Metabolism</i>. SAGE Publications. <a href=\"https://doi.org/10.1177/0271678X20965500\">https://doi.org/10.1177/0271678X20965500</a>","chicago":"Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé, et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” <i>Journal of Cerebral Blood Flow and Metabolism</i>. SAGE Publications, 2021. <a href=\"https://doi.org/10.1177/0271678X20965500\">https://doi.org/10.1177/0271678X20965500</a>.","ista":"Tournier N, Goutal S, Mairinger S, Lozano I, Filip T, Sauberer M, Caillé F, Breuil L, Stanek J, Freeman A, Novarino G, Truillet C, Wanek T, Langer O. 2021. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 41(7), 1634–1646.","ieee":"N. Tournier <i>et al.</i>, “Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” <i>Journal of Cerebral Blood Flow and Metabolism</i>, vol. 41, no. 7. SAGE Publications, pp. 1634–1646, 2021.","ama":"Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. <i>Journal of Cerebral Blood Flow and Metabolism</i>. 2021;41(7):1634-1646. doi:<a href=\"https://doi.org/10.1177/0271678X20965500\">10.1177/0271678X20965500</a>","short":"N. Tournier, S. Goutal, S. Mairinger, I. Lozano, T. Filip, M. Sauberer, F. Caillé, L. Breuil, J. Stanek, A. Freeman, G. Novarino, C. Truillet, T. Wanek, O. Langer, Journal of Cerebral Blood Flow and Metabolism 41 (2021) 1634–1646."},"oa_version":"Published Version","status":"public","department":[{"_id":"GaNo"}],"article_processing_charge":"No","month":"07","abstract":[{"lang":"eng","text":"P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict at the blood–brain barrier (BBB) the brain distribution of the majority of currently known molecularly targeted anticancer drugs. To improve brain delivery of dual ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques with PET. Tolerability of the erlotinib/tariquidar combination was assessed in human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3). Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar alone led to less pronounced VT,brain increases in both species. Treatment of cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly targeted anticancer drugs for a more effective treatment of brain tumors."}],"isi":1,"volume":41,"day":"01","external_id":{"pmid":["33081568"],"isi":["000664214100012"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"1634-1646","date_updated":"2026-06-18T19:36:17Z","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/"}],"oa":1,"publisher":"SAGE Publications","_id":"8730","author":[{"first_name":"N","full_name":"Tournier, N","last_name":"Tournier"},{"last_name":"Goutal","full_name":"Goutal, S","first_name":"S"},{"first_name":"S","last_name":"Mairinger","full_name":"Mairinger, S"},{"first_name":"IH","full_name":"Lozano, IH","last_name":"Lozano"},{"first_name":"T","last_name":"Filip","full_name":"Filip, T"},{"full_name":"Sauberer, M","last_name":"Sauberer","first_name":"M"},{"first_name":"F","last_name":"Caillé","full_name":"Caillé, F"},{"first_name":"L","last_name":"Breuil","full_name":"Breuil, L"},{"first_name":"J","full_name":"Stanek, J","last_name":"Stanek"},{"first_name":"AF","last_name":"Freeman","full_name":"Freeman, AF"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia"},{"first_name":"C","last_name":"Truillet","full_name":"Truillet, C"},{"first_name":"T","last_name":"Wanek","full_name":"Wanek, T"},{"full_name":"Langer, O","last_name":"Langer","first_name":"O"}],"ddc":["570"],"publication_status":"published","quality_controlled":"1"},{"status":"public","department":[{"_id":"GaNo"}],"volume":97,"month":"10","isi":1,"abstract":[{"lang":"eng","text":"Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal’s ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress."}],"article_processing_charge":"No","date_created":"2021-08-22T22:01:21Z","article_type":"original","citation":{"apa":"Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B., … Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. <i>Brain, Behavior, and Immunity</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.bbi.2021.07.022\">https://doi.org/10.1016/j.bbi.2021.07.022</a>","mla":"Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” <i>Brain, Behavior, and Immunity</i>, vol. 97, Elsevier, 2021, pp. 423–39, doi:<a href=\"https://doi.org/10.1016/j.bbi.2021.07.022\">10.1016/j.bbi.2021.07.022</a>.","chicago":"Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” <i>Brain, Behavior, and Immunity</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.bbi.2021.07.022\">https://doi.org/10.1016/j.bbi.2021.07.022</a>.","ieee":"K. Picard <i>et al.</i>, “Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice,” <i>Brain, Behavior, and Immunity</i>, vol. 97. Elsevier, pp. 423–439, 2021.","ista":"Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F, Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. 97, 423–439.","ama":"Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. <i>Brain, Behavior, and Immunity</i>. 2021;97:423-439. doi:<a href=\"https://doi.org/10.1016/j.bbi.2021.07.022\">10.1016/j.bbi.2021.07.022</a>","short":"K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F. Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C. Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain, Behavior, and Immunity 97 (2021) 423–439."},"oa_version":"Submitted Version","doi":"10.1016/j.bbi.2021.07.022","type":"journal_article","language":[{"iso":"eng"}],"date_published":"2021-10-01T00:00:00Z","publication":"Brain, Behavior, and Immunity","scopus_import":"1","intvolume":"        97","year":"2021","acknowledgement":"We acknowledge that Université Laval stands on the traditional and unceded land of the Huron-Wendat peoples; and that the University of Victoria exists on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ peoples have relationships to this land. We thank Emmanuel Planel for the access to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank the Centre for Advanced Materials and Related Technology for the access to the confocal microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from Fondation Famille-Choquette. K.B. was supported by excellence scholarships from Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S. were supported by postdoctoral fellowships from FRQS. This study was funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T. and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B, by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition.","publication_identifier":{"issn":["0889-1591"]},"pmid":1,"title":"Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice","publication_status":"published","quality_controlled":"1","oa":1,"publisher":"Elsevier","author":[{"first_name":"Katherine","last_name":"Picard","full_name":"Picard, Katherine"},{"last_name":"Bisht","full_name":"Bisht, Kanchan","first_name":"Kanchan"},{"first_name":"Silvia","full_name":"Poggini, Silvia","last_name":"Poggini"},{"full_name":"Garofalo, Stefano","last_name":"Garofalo","first_name":"Stefano"},{"full_name":"Golia, Maria Teresa","last_name":"Golia","first_name":"Maria Teresa"},{"last_name":"Basilico","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Abdallah","full_name":"Abdallah, Fatima","first_name":"Fatima"},{"last_name":"Ciano Albanese","full_name":"Ciano Albanese, Naomi","first_name":"Naomi"},{"first_name":"Irmgard","last_name":"Amrein","full_name":"Amrein, Irmgard"},{"first_name":"Nathalie","full_name":"Vernoux, Nathalie","last_name":"Vernoux"},{"full_name":"Sharma, Kaushik","last_name":"Sharma","first_name":"Kaushik"},{"first_name":"Chin Wai","full_name":"Hui, Chin Wai","last_name":"Hui"},{"last_name":"C. Savage","full_name":"C. Savage, Julie","first_name":"Julie"},{"full_name":"Limatola, Cristina","last_name":"Limatola","first_name":"Cristina"},{"first_name":"Davide","last_name":"Ragozzino","full_name":"Ragozzino, Davide"},{"first_name":"Laura","full_name":"Maggi, Laura","last_name":"Maggi"},{"first_name":"Igor","last_name":"Branchi","full_name":"Branchi, Igor"},{"full_name":"Tremblay, Marie Ève","last_name":"Tremblay","first_name":"Marie Ève"}],"_id":"9953","page":"423-439","date_updated":"2023-10-03T09:49:18Z","main_file_link":[{"url":"https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf","open_access":"1"}],"external_id":{"pmid":["34343616"],"isi":["000702878400007"]},"day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"oa":1,"file_date_updated":"2021-05-28T12:39:43Z","publisher":"Springer Nature","author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell","full_name":"Morandell, Jasmin"},{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A","last_name":"Schwarz","full_name":"Schwarz, Lena A"},{"orcid":"0000-0003-1843-3173","last_name":"Basilico","full_name":"Basilico, Bernadette","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","last_name":"Tasciyan","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren"},{"id":"38C393BE-F248-11E8-B48F-1D18A9856A87","first_name":"Georgi A","orcid":"0000-0001-8370-6161","last_name":"Dimchev","full_name":"Dimchev, Georgi A"},{"full_name":"Nicolas, Armel","last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105"},{"full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger","first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Dotter","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe","last_name":"Dobler","full_name":"Dobler, Zoe"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","last_name":"Schur","orcid":"0000-0003-4790-8078"},{"full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"_id":"9429","ddc":["572"],"has_accepted_license":"1","publication_status":"published","quality_controlled":"1","corr_author":"1","day":"24","external_id":{"isi":["000658769900010"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"},{"grant_number":"F7807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem cells in autism and epilepsy"},{"name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","call_identifier":"FWF"}],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"date_updated":"2026-06-26T22:30:54Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"article_type":"original","date_created":"2021-05-28T11:49:46Z","acknowledged_ssus":[{"_id":"PreCl"}],"citation":{"ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>.","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>"},"oa_version":"Published Version","file":[{"checksum":"337e0f7959c35ec959984cacdcb472ba","success":1,"content_type":"application/pdf","file_name":"2021_NatureCommunications_Morandell.pdf","date_updated":"2021-05-28T12:39:43Z","file_size":9358599,"access_level":"open_access","file_id":"9430","date_created":"2021-05-28T12:39:43Z","creator":"kschuh","relation":"main_file"}],"status":"public","related_material":{"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}],"record":[{"id":"19557","status":"public","relation":"dissertation_contains"},{"id":"7800","status":"public","relation":"earlier_version"},{"relation":"dissertation_contains","status":"public","id":"12401"}]},"department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"article_processing_charge":"No","isi":1,"month":"05","abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"volume":12,"year":"2021","intvolume":"        12","acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","issue":"1","publication_identifier":{"eissn":["2041-1723"]},"article_number":"3058","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","doi":"10.1038/s41467-021-23123-x","type":"journal_article","scopus_import":"1","language":[{"iso":"eng"}],"publication":"Nature Communications","date_published":"2021-05-24T00:00:00Z"}]