[{"day":"01","citation":{"apa":"Miteva, F. E., Maes, M. E., Alamalhoda, M., Firoozi, A., Colombo, G., &#38; Siegert, S. (2025). Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye. <i>Investigative Ophthalmology &#38; Visual Science</i>. Association for Research in Vision and Ophthalmology. <a href=\"https://doi.org/10.1167/iovs.66.3.49\">https://doi.org/10.1167/iovs.66.3.49</a>","mla":"Miteva, Florianne E., et al. “Optic Nerve Crush Does Not Induce Retinal Ganglion Cell Loss in the Contralateral Eye.” <i>Investigative Ophthalmology &#38; Visual Science</i>, vol. 66, no. 3, 49, Association for Research in Vision and Ophthalmology, 2025, doi:<a href=\"https://doi.org/10.1167/iovs.66.3.49\">10.1167/iovs.66.3.49</a>.","short":"F.E. Miteva, M.E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, S. Siegert, Investigative Ophthalmology &#38; Visual Science 66 (2025).","ieee":"F. E. Miteva, M. E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, and S. Siegert, “Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye,” <i>Investigative Ophthalmology &#38; Visual Science</i>, vol. 66, no. 3. Association for Research in Vision and Ophthalmology, 2025.","chicago":"Miteva, Florianne E, Margaret E Maes, Mohammad Alamalhoda, Arsalan Firoozi, Gloria Colombo, and Sandra Siegert. “Optic Nerve Crush Does Not Induce Retinal Ganglion Cell Loss in the Contralateral Eye.” <i>Investigative Ophthalmology &#38; Visual Science</i>. Association for Research in Vision and Ophthalmology, 2025. <a href=\"https://doi.org/10.1167/iovs.66.3.49\">https://doi.org/10.1167/iovs.66.3.49</a>.","ama":"Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye. <i>Investigative Ophthalmology &#38; Visual Science</i>. 2025;66(3). doi:<a href=\"https://doi.org/10.1167/iovs.66.3.49\">10.1167/iovs.66.3.49</a>","ista":"Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. 2025. Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye. Investigative Ophthalmology &#38; Visual Science. 66(3), 49."},"has_accepted_license":"1","external_id":{"pmid":["40126507"]},"abstract":[{"lang":"eng","text":"Purpose: Optic nerve crush (ONC) is a model for studying optic nerve trauma. Unilateral ONC induces massive retinal ganglion cell (RGC) degeneration in the affected eye, leading to vision loss within a month. A common assumption has been that the non-injured contralateral eye is unaffected due to the minimal retino-retinal projections of the RGCs at the chiasm. Yet, recently, microglia, the brain-resident macrophages, have shown a responsive phenotype in the contralateral eye after ONC. Whether RGC loss accompanies this phenotype is still controversial.\r\n\r\nMethods: Using the available RGCode algorithm and developing our own RGC-Quant deep-learning-based tool, we quantify RGC's total number and density across the entire retina after ONC.\r\n\r\nResults: We confirm a short-term microglia response in the contralateral eye after ONC, but this did not affect the microglia number. Furthermore, we cannot confirm the previously reported RGC loss between naïve and contralateral retinas 5 weeks after ONC induction across the commonly used Cx3cr1creERT2 and C57BL6/J mouse models. Neither sex nor the direct comparison of the RGC markers Brn3a and RBPMS, with Brn3a co-labeling, on average, 89% of the RBPMS+-cells, explained this discrepancy, suggesting that the early microglia-responsive phenotype does not have immediate consequences on the RGC number.\r\n\r\nConclusions: Our results corroborate that unilateral optic nerve injury elicits a microglial response in the uninjured contralateral eye but without RGC loss. Therefore, the contralateral eye should be treated separately and not as an ONC control."}],"_id":"19566","language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","OA_place":"publisher","date_published":"2025-03-01T00:00:00Z","article_number":"49","intvolume":"        66","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"year":"2025","date_updated":"2026-04-07T12:00:41Z","publication":"Investigative Ophthalmology & Visual Science","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"file_date_updated":"2025-04-15T13:49:10Z","DOAJ_listed":"1","issue":"3","scopus_import":"1","status":"public","file":[{"success":1,"content_type":"application/pdf","file_size":2721477,"date_created":"2025-04-15T13:49:10Z","access_level":"open_access","relation":"main_file","creator":"dernst","date_updated":"2025-04-15T13:49:10Z","file_id":"19567","checksum":"e8722ce5792f6c08fe1e191f7de6f147","file_name":"2025_IOVS_SchootUiterkamp.pdf"}],"publication_status":"published","title":"Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye","date_created":"2025-04-15T13:40:35Z","OA_type":"gold","oa_version":"Published Version","publication_identifier":{"issn":["1552-5783"]},"volume":66,"author":[{"id":"3526230C-F248-11E8-B48F-1D18A9856A87","first_name":"Florianne E","last_name":"Schoot Uiterkamp","full_name":"Schoot Uiterkamp, Florianne E"},{"first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9642-1085","full_name":"Maes, Margaret E","last_name":"Maes"},{"first_name":"Mohammad","last_name":"Alamalhoda","full_name":"Alamalhoda, Mohammad"},{"first_name":"Arsalan","full_name":"Firoozi, Arsalan","last_name":"Firoozi"},{"first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","last_name":"Colombo","full_name":"Colombo, Gloria"},{"full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra"}],"department":[{"_id":"SaSi"}],"month":"03","project":[{"name":"Dissecting the morpho-functional relationship of microglia","grant_number":"P37131","_id":"7be82147-9f16-11ee-852c-f44682d73140"},{"name":"FWF Open Access Fund","call_identifier":"FWF","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1"}],"article_type":"original","doi":"10.1167/iovs.66.3.49","oa":1,"acknowledgement":"The authors thank the Scientific Service Units (SSU) of ISTA for the provided resources, specifically the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger, Claudia Gold, and Michael Schunn, for mouse colony management and support. We thank all members of the Siegert group for constant feedback on the project and the manuscript. \r\nSupported in whole or in part by the Austrian Science Fund (FWF) [10.55776/P37131]. For open access purposes, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission. ","related_material":{"link":[{"url":"https://github.com/siegert-lab/RGC-Quant","relation":"software"}],"record":[{"status":"public","id":"20467","relation":"dissertation_contains"}]},"pmid":1,"article_processing_charge":"Yes","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","publisher":"Association for Research in Vision and Ophthalmology"},{"department":[{"_id":"SaSi"}],"month":"04","article_type":"original","project":[{"_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","grant_number":"SC19-017","name":"How human microglia shape developing neurons during health and inflammation"}],"author":[{"first_name":"Verena","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","last_name":"Hübschmann","full_name":"Hübschmann, Verena"},{"last_name":"Korkut","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","first_name":"Medina","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"last_name":"Maya-Arteaga","full_name":"Maya-Arteaga, Juan Pablo","first_name":"Juan Pablo","id":"c815d433-1f5d-11f0-a875-dad18b1e5924"},{"full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"volume":22,"oa":1,"doi":"10.1186/s12974-025-03366-x","acknowledgement":"We thank the scientific service units at ISTA, specifically the Lab Support Facility (LSF), the Molecular Biology Services/Virus Services Team, specifically Flavia Gama Gomes Leite and Mark Andrew Smyth, for the virus production, and the Imaging and Optics Facility (IOF). We thank all members of the Siegert group and Marco Benevento for their constant feedback on the project and comments on the manuscript. A special thanks to Rouven Schulz for input on statistical analysis and sharing R-scripts, Gloria Colombo for the introduction to cell sorting, Negar Vehdani and Florianne Schoot Uiterkamp for their support in cell culture. This research was supported by the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.).","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"20074"}],"link":[{"url":"https://ista.ac.at/en/news/pink-skies/","relation":"press_release","description":"News on ISTA website"}]},"pmid":1,"publisher":"Springer Nature","article_processing_charge":"Yes","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","file":[{"success":1,"content_type":"application/pdf","file_size":4482167,"date_created":"2025-04-22T09:46:27Z","access_level":"open_access","file_id":"19607","relation":"main_file","creator":"dernst","date_updated":"2025-04-22T09:46:27Z","checksum":"dcc355c21ab713e45fda5c61b5fa5299","file_name":"2025_JourNeuroinflammation_Schmied.pdf"}],"publication_status":"published","OA_type":"gold","oa_version":"Published Version","date_created":"2025-04-20T22:01:28Z","title":"Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids","publication_identifier":{"eissn":["1742-2094"]},"isi":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"date_updated":"2026-04-28T13:38:26Z","publication":"Journal of Neuroinflammation","file_date_updated":"2025-04-22T09:46:27Z","scopus_import":"1","DOAJ_listed":"1","issue":"1","status":"public","PlanS_conform":"1","citation":{"ista":"Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. 2025. Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids. Journal of Neuroinflammation. 22(1), 98.","ama":"Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids. <i>Journal of Neuroinflammation</i>. 2025;22(1). doi:<a href=\"https://doi.org/10.1186/s12974-025-03366-x\">10.1186/s12974-025-03366-x</a>","chicago":"Schmied, Verena, Medina Korkut, Alessandro Venturino, Juan Pablo Maya-Arteaga, and Sandra Siegert. “Microglia Determine an Immune-Challenged Environment and Facilitate Ibuprofen Action in Human Retinal Organoids.” <i>Journal of Neuroinflammation</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1186/s12974-025-03366-x\">https://doi.org/10.1186/s12974-025-03366-x</a>.","ieee":"V. Schmied, M. Korkut, A. Venturino, J. P. Maya-Arteaga, and S. Siegert, “Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids,” <i>Journal of Neuroinflammation</i>, vol. 22, no. 1. Springer Nature, 2025.","short":"V. Schmied, M. Korkut, A. Venturino, J.P. Maya-Arteaga, S. Siegert, Journal of Neuroinflammation 22 (2025).","mla":"Schmied, Verena, et al. “Microglia Determine an Immune-Challenged Environment and Facilitate Ibuprofen Action in Human Retinal Organoids.” <i>Journal of Neuroinflammation</i>, vol. 22, no. 1, 98, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1186/s12974-025-03366-x\">10.1186/s12974-025-03366-x</a>.","apa":"Schmied, V., Korkut, M., Venturino, A., Maya-Arteaga, J. P., &#38; Siegert, S. (2025). Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids. <i>Journal of Neuroinflammation</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s12974-025-03366-x\">https://doi.org/10.1186/s12974-025-03366-x</a>"},"day":"03","has_accepted_license":"1","quality_controlled":"1","type":"journal_article","external_id":{"pmid":["40181459"],"isi":["001459311800002"]},"_id":"19593","language":[{"iso":"eng"}],"abstract":[{"text":"Prenatal immune challenges pose significant risks to human embryonic brain and eye development. However, our knowledge about the safe usage of anti-inflammatory drugs during pregnancy is still limited. While human induced pluripotent stem cells (hIPSC)-derived brain organoid models have started to explore functional consequences upon viral stimulation, these models commonly lack microglia, which are susceptible to and promote inflammation. Furthermore, microglia are actively involved in neuronal development. Here, we generate hIPSC-derived microglia precursor cells and assemble them into retinal organoids. Once the outer plexiform layer forms, these hIPSC-derived microglia (iMG) fully integrate into the retinal organoids. Since the ganglion cell survival declines by this time in 3D-retinal organoids, we adapted the model into 2D and identify that the improved ganglion cell number significantly decreases only with iMG presence. In parallel, we applied the immunostimulant POLY(I:C) to mimic a fetal viral infection. While POLY(I:C) exposure alters the iMG phenotype, it does not hinder their interaction with ganglion cells. Furthermore, iMG significantly enhance the supernatant’s inflammatory secretome and increase retinal cell proliferation. Simultaneous exposure with the non-steroidal anti-inflammatory drug (NSAID) ibuprofen dampens POLY(I:C)-mediated changes of the iMG phenotype and ameliorates cell proliferation. Remarkably, while POLY(I:C) disrupts neuronal calcium dynamics independent of iMG, ibuprofen rescues this effect only if iMG are present. Mechanistically, ibuprofen targets the enzymes cyclooxygenase 1 and 2 (COX1/PTGS1 and COX2/PTGS2) simultaneously, from which iMG mainly express COX1. Selective COX1 blockage fails to restore the calcium peak amplitude upon POLY(I:C) stimulation, suggesting ibuprofen’s beneficial effect depends on the presence and interplay of COX1 and COX2. These findings underscore the importance of microglia in the context of prenatal immune challenges and provide insight into the mechanisms by which ibuprofen exerts its protective effects during embryonic development.","lang":"eng"}],"OA_place":"publisher","date_published":"2025-04-03T00:00:00Z","ddc":["570"],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","year":"2025","article_number":"98","intvolume":"        22"},{"page":"1051-1064","status":"public","scopus_import":"1","ec_funded":1,"file_date_updated":"2025-01-09T07:48:01Z","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"isi":1,"date_updated":"2026-04-14T08:34:35Z","publication":"Nature Biotechnology","year":"2024","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"        42","date_published":"2024-07-01T00:00:00Z","OA_place":"publisher","type":"journal_article","quality_controlled":"1","_id":"14257","language":[{"iso":"eng"}],"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 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."}],"external_id":{"isi":["001065254200001"],"pmid":["37653226"]},"has_accepted_license":"1","citation":{"mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, vol. 42, Springer Nature, 2024, pp. 1051–64, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>, vol. 42. Springer Nature, pp. 1051–1064, 2024.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2024;42:1051-1064. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 42, 1051–1064.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>."},"day":"01","publisher":"Springer Nature","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"Yes (in subscription journal)","pmid":1,"related_material":{"record":[{"status":"deleted","id":"18660","relation":"dissertation_contains"},{"relation":"research_data","status":"public","id":"13126"},{"status":"public","id":"18674","relation":"dissertation_contains"}],"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}]},"acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","oa":1,"doi":"10.1038/s41587-023-01911-8","project":[{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"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"},{"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","grant_number":"715508"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","grant_number":"101026635"}],"article_type":"original","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"month":"07","volume":42,"author":[{"full_name":"Michalska, Julia M","last_name":"Michalska","orcid":"0000-0003-3862-1235","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Velicky, Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","orcid":"0000-0002-2340-7431"},{"first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova","full_name":"Korinkova, Hana"},{"last_name":"Watson","full_name":"Watson, Jake","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"full_name":"Amberg, Nicole","last_name":"Amberg","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole"},{"orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"first_name":"Romana","last_name":"Höftberger","full_name":"Höftberger, Romana"},{"last_name":"Siegert","full_name":"Siegert, Sandra","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"},{"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","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl"}],"publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"oa_version":"Published Version","OA_type":"hybrid","title":"Imaging brain tissue architecture across millimeter to nanometer scales","date_created":"2023-09-03T22:01:15Z","publication_status":"published","file":[{"checksum":"57d5fafb16f02dcb9f7dddb1bd7e2a71","file_name":"2024_NatureBiotech_Michalska.pdf","date_updated":"2025-01-09T07:48:01Z","creator":"dernst","relation":"main_file","file_id":"18784","access_level":"open_access","content_type":"application/pdf","success":1,"file_size":26065165,"date_created":"2025-01-09T07:48:01Z"}]},{"publication_identifier":{"eissn":["2589-0042"]},"oa_version":"Published Version","title":"Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout","date_created":"2023-09-24T22:01:11Z","publication_status":"published","file":[{"checksum":"be1a560efdd96d20712311f4fc54aac2","file_name":"2023_iScience_Maes.pdf","relation":"main_file","creator":"dernst","date_updated":"2023-11-07T08:53:21Z","file_id":"14497","access_level":"open_access","content_type":"application/pdf","success":1,"file_size":8197935,"date_created":"2023-11-07T08:53:21Z"}],"publisher":"Elsevier","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","article_processing_charge":"Yes","pmid":1,"acknowledgement":"We thank the Scientific Service Units (SSU) of ISTA through resources provided by the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger and Michael Schunn for excellent mouse colony management and support. This research was supported by the FWF Sonderforschungsbereich F83 (to E.E.P). We thank Bálint Nagy, Ryan John A. Cubero, Marco Benevento and all members of the Siegert group for constant feedback on the project and article.","doi":"10.1016/j.isci.2023.107780","oa":1,"article_type":"original","department":[{"_id":"SaSi"}],"month":"10","author":[{"full_name":"Maes, Margaret E","last_name":"Maes","orcid":"0000-0001-9642-1085","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","last_name":"Colombo"},{"first_name":"Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","last_name":"Schoot Uiterkamp","full_name":"Schoot Uiterkamp, Florianne E"},{"first_name":"Felix","full_name":"Sternberg, Felix","last_name":"Sternberg"},{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"first_name":"Elena E.","last_name":"Pohl","full_name":"Pohl, Elena E."},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra"}],"volume":26,"year":"2023","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"article_number":"107780","intvolume":"        26","date_published":"2023-10-20T00:00:00Z","type":"journal_article","quality_controlled":"1","_id":"14363","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Mitochondrial networks remodel their connectivity, content, and subcellular localization to support optimized energy production in conditions of increased environmental or cellular stress. Microglia rely on mitochondria to respond to these stressors, however our knowledge about mitochondrial networks and their adaptations in microglia in vivo is limited. Here, we generate a mouse model that selectively labels mitochondria in microglia. We identify that mitochondrial networks are more fragmented with increased content and perinuclear localization in vitro vs. in vivo. Mitochondrial networks adapt similarly in microglia closest to the injury site after optic nerve crush. Preventing microglial UCP2 increase after injury by selective knockout induces cellular stress. This results in mitochondrial hyperfusion in male microglia, a phenotype absent in females due to circulating estrogens. Our results establish the foundation for mitochondrial network analysis of microglia in vivo, emphasizing the importance of mitochondrial-based sex effects of microglia in other pathologies."}],"external_id":{"pmid":["37731609"],"isi":["001080403500001"]},"has_accepted_license":"1","day":"20","citation":{"mla":"Maes, Margaret E., et al. “Mitochondrial Network Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and UCP2 Knockout.” <i>IScience</i>, vol. 26, no. 10, 107780, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.isci.2023.107780\">10.1016/j.isci.2023.107780</a>.","ieee":"M. E. Maes <i>et al.</i>, “Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout,” <i>iScience</i>, vol. 26, no. 10. Elsevier, 2023.","short":"M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino, E.E. Pohl, S. Siegert, IScience 26 (2023).","apa":"Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino, A., Pohl, E. E., &#38; Siegert, S. (2023). Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. <i>IScience</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.isci.2023.107780\">https://doi.org/10.1016/j.isci.2023.107780</a>","ama":"Maes ME, Colombo G, Schoot Uiterkamp FE, et al. Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. <i>iScience</i>. 2023;26(10). doi:<a href=\"https://doi.org/10.1016/j.isci.2023.107780\">10.1016/j.isci.2023.107780</a>","ista":"Maes ME, Colombo G, Schoot Uiterkamp FE, Sternberg F, Venturino A, Pohl EE, Siegert S. 2023. Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. iScience. 26(10), 107780.","chicago":"Maes, Margaret E, Gloria Colombo, Florianne E Schoot Uiterkamp, Felix Sternberg, Alessandro Venturino, Elena E. Pohl, and Sandra Siegert. “Mitochondrial Network Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and UCP2 Knockout.” <i>IScience</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.isci.2023.107780\">https://doi.org/10.1016/j.isci.2023.107780</a>."},"status":"public","scopus_import":"1","issue":"10","file_date_updated":"2023-11-07T08:53:21Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"isi":1,"date_updated":"2024-10-09T21:07:01Z","publication":"iScience"},{"file_date_updated":"2023-01-23T09:50:51Z","acknowledged_ssus":[{"_id":"Bio"}],"publication":"STAR Protocols","date_updated":"2025-06-11T13:58:47Z","status":"public","scopus_import":"1","ec_funded":1,"issue":"4","quality_controlled":"1","type":"journal_article","external_id":{"pmid":["36595902"]},"abstract":[{"text":"To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.\r\nFor complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1","lang":"eng"}],"_id":"12117","language":[{"iso":"eng"}],"citation":{"apa":"Hübschmann, V., Korkut, M., &#38; Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>","short":"V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).","ieee":"V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” <i>STAR Protocols</i>, vol. 3, no. 4. Elsevier, 2022.","mla":"Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>, vol. 3, no. 4, 101866, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>.","chicago":"Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>.","ista":"Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 3(4), 101866.","ama":"Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. 2022;3(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>"},"day":"16","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"year":"2022","intvolume":"         3","article_number":"101866","date_published":"2022-12-16T00:00:00Z","doi":"10.1016/j.xpro.2022.101866","oa":1,"acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for their insights into functional assays and data analysis, Verena Seiboth for insights into necessary institutional permission, and ISTA imaging & optics facility (IOF) especially Bernhard Hochreiter for their support.","department":[{"_id":"SaSi"},{"_id":"GradSch"}],"month":"12","project":[{"grant_number":"715571","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease"},{"_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","grant_number":"SC19-017","name":"How human microglia shape developing neurons during health and inflammation"}],"article_type":"letter_note","author":[{"first_name":"Verena","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","last_name":"Hübschmann","full_name":"Hübschmann, Verena"},{"last_name":"Korkut","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","first_name":"Medina"},{"last_name":"Siegert","full_name":"Siegert, Sandra","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"volume":3,"publisher":"Elsevier","article_processing_charge":"No","corr_author":"1","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"related_material":{"record":[{"status":"public","id":"11478","relation":"other"}]},"pmid":1,"publication_status":"published","file":[{"file_size":6251945,"date_created":"2023-01-23T09:50:51Z","success":1,"content_type":"application/pdf","access_level":"open_access","date_updated":"2023-01-23T09:50:51Z","file_id":"12340","relation":"main_file","creator":"dernst","file_name":"2022_STARProtocols_Huebschmann.pdf","checksum":"3c71b8a60633d42c2f77c49025d5559b"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"publication_identifier":{"issn":["2666-1667"]},"oa_version":"Published Version","date_created":"2023-01-12T11:56:38Z","title":"Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay"},{"publication_status":"published","file":[{"relation":"main_file","date_updated":"2022-07-04T08:19:25Z","creator":"cchlebak","file_id":"11480","file_name":"2022_iScience_Bartalska.pdf","checksum":"a470b74e1b3796c710189c81a4cd4329","file_size":19400048,"date_created":"2022-07-04T08:19:25Z","success":1,"content_type":"application/pdf","access_level":"open_access"}],"publication_identifier":{"eissn":["2589-0042"]},"title":"A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation","date_created":"2022-07-03T22:01:33Z","oa_version":"Published Version","acknowledgement":"We thank the scientific service units at ISTA, specifically the lab support facility and imaging & optics facility for their support; Nicolas Armel for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner for their help in human brain tissue collection, Rouven Schulz for his insights into the functional assays We thank all members of the Siegert group for constant feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for feedback on the manuscript. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.).","oa":1,"doi":"10.1016/j.isci.2022.104580","author":[{"first_name":"Katarina","id":"4D883232-F248-11E8-B48F-1D18A9856A87","full_name":"Bartalska, Katarina","last_name":"Bartalska"},{"full_name":"Hübschmann, Verena","last_name":"Hübschmann","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","first_name":"Verena"},{"full_name":"Korkut, Medina","last_name":"Korkut","orcid":"0000-0003-4309-2251","first_name":"Medina","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0002-1867","first_name":"Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425","full_name":"Cubero, Ryan J","last_name":"Cubero"},{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino"},{"full_name":"Rössler, Karl","last_name":"Rössler","first_name":"Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","full_name":"Siegert, Sandra"}],"volume":25,"article_type":"original","project":[{"name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"},{"_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","grant_number":"SC19-017","name":"How human microglia shape developing neurons during health and inflammation"}],"month":"07","department":[{"_id":"SaSi"}],"corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"Yes","publisher":"Elsevier","pmid":1,"related_material":{"record":[{"status":"public","id":"12117","relation":"other"},{"id":"20074","status":"public","relation":"dissertation_contains"}]},"language":[{"iso":"eng"}],"_id":"11478","abstract":[{"lang":"eng","text":"Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain."}],"external_id":{"isi":["000830428500005"],"pmid":["35789843"]},"type":"journal_article","quality_controlled":"1","has_accepted_license":"1","day":"15","citation":{"apa":"Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler, K., … Siegert, S. (2022). A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. <i>IScience</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.isci.2022.104580\">https://doi.org/10.1016/j.isci.2022.104580</a>","mla":"Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>, vol. 25, no. 7, 104580, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.isci.2022.104580\">10.1016/j.isci.2022.104580</a>.","short":"K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler, T. Czech, S. Siegert, IScience 25 (2022).","ieee":"K. Bartalska <i>et al.</i>, “A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation,” <i>iScience</i>, vol. 25, no. 7. Elsevier, 2022.","chicago":"Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.isci.2022.104580\">https://doi.org/10.1016/j.isci.2022.104580</a>.","ama":"Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. <i>iScience</i>. 2022;25(7). doi:<a href=\"https://doi.org/10.1016/j.isci.2022.104580\">10.1016/j.isci.2022.104580</a>","ista":"Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 25(7), 104580."},"intvolume":"        25","article_number":"104580","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["610"],"date_published":"2022-07-15T00:00:00Z","file_date_updated":"2022-07-04T08:19:25Z","publication":"iScience","date_updated":"2026-04-07T11:51:43Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"isi":1,"status":"public","ec_funded":1,"issue":"7","scopus_import":"1"},{"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"isi":1,"publication":"Nature Communications","date_updated":"2026-04-07T14:17:58Z","file_date_updated":"2022-08-29T06:44:30Z","scopus_import":"1","status":"public","has_accepted_license":"1","day":"15","citation":{"apa":"Schulz, R., Korkut, M., Venturino, A., Colombo, G., &#38; Siegert, S. (2022). Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>","mla":"Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>, vol. 13, 4728, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>.","ieee":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","short":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022).","chicago":"Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>.","ama":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>","ista":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. 13, 4728."},"type":"journal_article","quality_controlled":"1","abstract":[{"text":"G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest. We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we included two additional DREADD-based chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands.","lang":"eng"}],"_id":"11995","language":[{"iso":"eng"}],"external_id":{"pmid":["35970889"],"isi":["000840984400032"]},"date_published":"2022-08-15T00:00:00Z","year":"2022","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_number":"4728","intvolume":"        13","project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"article_type":"original","department":[{"_id":"SaSi"}],"month":"08","author":[{"full_name":"Schulz, Rouven","last_name":"Schulz","orcid":"0000-0001-5297-733X","first_name":"Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Korkut","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","first_name":"Medina"},{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"orcid":"0000-0001-9434-8902","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","last_name":"Colombo","full_name":"Colombo, Gloria"},{"orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","last_name":"Siegert"}],"volume":13,"acknowledgement":"The authors thank the Scientific Service Units at ISTA, in particular the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility, and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco Benevento for sharing reagents and expertise. This research was supported by a DOC Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.","oa":1,"doi":"10.1038/s41467-022-32390-1","pmid":1,"related_material":{"link":[{"relation":"press_release","description":"News on ISTA website","url":"https://ista.ac.at/en/news/dreaddful-mimicry/"}],"record":[{"relation":"research_data","status":"public","id":"11542"},{"status":"public","id":"11945","relation":"part_of_dissertation"}]},"publisher":"Springer Nature","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"No","file":[{"checksum":"191d9db0266e14a28d3a56dc7f65da84","file_name":"2022_NatComm_Schulz.pdf","date_updated":"2022-08-29T06:44:30Z","creator":"cchlebak","file_id":"12002","relation":"main_file","access_level":"open_access","success":1,"content_type":"application/pdf","file_size":7317396,"date_created":"2022-08-29T06:44:30Z"}],"publication_status":"published","oa_version":"Published Version","title":"Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses","date_created":"2022-08-28T22:01:59Z","publication_identifier":{"eissn":["2041-1723"]}},{"year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"date_published":"2022-08-18T00:00:00Z","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","date_created":"2022-08-24T08:24:52Z","type":"preprint","publication_status":"draft","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."}],"_id":"11950","language":[{"iso":"eng"}],"day":"18","citation":{"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.).","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.","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>","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>.","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>","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>."},"publisher":"Cold Spring Harbor Laboratory","status":"public","corr_author":"1","article_processing_charge":"No","related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"oa":1,"doi":"10.1101/2022.08.17.504272","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"month":"08","date_updated":"2026-04-27T22:30:32Z","publication":"bioRxiv","author":[{"full_name":"Michalska, Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","orcid":"0000-0003-3862-1235"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-2340-7431","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","full_name":"Velicky, Philipp"},{"last_name":"Korinkova","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana"},{"full_name":"Watson, Jake","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Venturino, Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}]},{"scopus_import":"1","ec_funded":1,"issue":"10","page":"1379-1393","status":"public","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"isi":1,"publication":"Nature Neuroscience","date_updated":"2026-04-27T22:30:34Z","file_date_updated":"2023-01-30T08:06:56Z","date_published":"2022-10-01T00:00:00Z","year":"2022","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"intvolume":"        25","has_accepted_license":"1","citation":{"ista":"Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience. 25(10), 1379–1393.","ama":"Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. 2022;25(10):1379-1393. doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>","chicago":"Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>.","ieee":"G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.","short":"G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero, J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature Neuroscience 25 (2022) 1379–1393.","mla":"Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>.","apa":"Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>"},"day":"01","type":"journal_article","quality_controlled":"1","abstract":[{"text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology.","lang":"eng"}],"_id":"12244","language":[{"iso":"eng"}],"external_id":{"isi":["000862214700001"],"pmid":["36180790"]},"pmid":1,"related_material":{"link":[{"url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/","description":"News on ISTA website","relation":"press_release"}],"record":[{"id":"12378","status":"public","relation":"dissertation_contains"}]},"publisher":"Springer Nature","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","article_processing_charge":"No","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715571"}],"article_type":"original","month":"10","department":[{"_id":"SaSi"}],"author":[{"first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","last_name":"Colombo","full_name":"Colombo, Gloria"},{"last_name":"Cubero","full_name":"Cubero, Ryan J","orcid":"0000-0003-0002-1867","id":"850B2E12-9CD4-11E9-837F-E719E6697425","first_name":"Ryan J"},{"last_name":"Kanari","full_name":"Kanari, Lida","first_name":"Lida"},{"first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"full_name":"Schulz, Rouven","last_name":"Schulz","orcid":"0000-0001-5297-733X","first_name":"Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Martina","last_name":"Scolamiero","full_name":"Scolamiero, Martina"},{"last_name":"Agerberg","full_name":"Agerberg, Jens","first_name":"Jens"},{"first_name":"Hansruedi","last_name":"Mathys","full_name":"Mathys, Hansruedi"},{"full_name":"Tsai, Li-Huei","last_name":"Tsai","first_name":"Li-Huei"},{"first_name":"Wojciech","full_name":"Chachólski, Wojciech","last_name":"Chachólski"},{"full_name":"Hess, Kathryn","last_name":"Hess","first_name":"Kathryn"},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"volume":25,"acknowledgement":"We thank the scientific service units at ISTA, in particular M. Schunn’s team at the preclinical facility, and especially our colony manager S. Haslinger, for excellent support. We are also grateful to the ISTA Imaging & Optics Facility, and in particular C. Sommer for helping with the data file conversions. We thank R. Erhart from the ISTA Scientific Computing Unit for improving the script performance. We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert group for constant feedback on the project and on the manuscript. This research was supported by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","oa":1,"doi":"10.1038/s41593-022-01167-6","oa_version":"Published Version","title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","date_created":"2023-01-16T09:53:07Z","publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"keyword":["General Neuroscience"],"file":[{"file_id":"12437","relation":"main_file","date_updated":"2023-01-30T08:06:56Z","creator":"dernst","file_name":"2022_NatureNeuroscience_Colombo.pdf","checksum":"28431146873096f52e0107b534f178c9","file_size":23789835,"date_created":"2023-01-30T08:06:56Z","success":1,"content_type":"application/pdf","access_level":"open_access"}],"publication_status":"published"},{"month":"12","department":[{"_id":"SaSi"}],"article_type":"original","project":[{"name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425"}],"author":[{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","last_name":"Venturino"},{"orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","full_name":"Siegert, Sandra"}],"volume":2,"oa":1,"doi":"10.1016/j.xpro.2021.101012","acknowledgement":"This research was supported by the European Research Council (grant 715571 to S.S.). We thank Rouven Schulz, Michael Schunn, Claudia Gold, Gabriel Krens, Sarah Gorkiewicz, Margaret Maes, Jürgen Siegert, Marco Benevento, and Sara Oakeley for comments on the manuscript and the IST Austria Bioimaging Facility for the technical support.","publisher":"Elsevier","article_processing_charge":"Yes","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"file":[{"creator":"cchlebak","file_id":"10570","date_updated":"2021-12-20T08:58:40Z","relation":"main_file","file_name":"2021_STARProt_Venturino.pdf","checksum":"9ea2501056c5df99e84726b845e9b976","date_created":"2021-12-20T08:58:40Z","file_size":6207060,"success":1,"content_type":"application/pdf","access_level":"open_access"}],"publication_status":"published","oa_version":"Published Version","date_created":"2021-12-19T23:01:32Z","title":"Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain","publication_identifier":{"eissn":["2666-1667"]},"acknowledged_ssus":[{"_id":"Bio"}],"publication":"STAR Protocols","date_updated":"2025-05-14T11:26:30Z","file_date_updated":"2021-12-20T08:58:40Z","scopus_import":"1","ec_funded":1,"issue":"4","status":"public","day":"17","citation":{"ista":"Venturino A, Siegert S. 2021. Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols. 2(4), 101012.","ama":"Venturino A, Siegert S. Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. <i>STAR Protocols</i>. 2021;2(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">10.1016/j.xpro.2021.101012</a>","chicago":"Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.” <i>STAR Protocols</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">https://doi.org/10.1016/j.xpro.2021.101012</a>.","short":"A. Venturino, S. Siegert, STAR Protocols 2 (2021).","ieee":"A. Venturino and S. Siegert, “Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain,” <i>STAR Protocols</i>, vol. 2, no. 4. Elsevier, 2021.","mla":"Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.” <i>STAR Protocols</i>, vol. 2, no. 4, 101012, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">10.1016/j.xpro.2021.101012</a>.","apa":"Venturino, A., &#38; Siegert, S. (2021). Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">https://doi.org/10.1016/j.xpro.2021.101012</a>"},"has_accepted_license":"1","quality_controlled":"1","type":"journal_article","_id":"10565","abstract":[{"lang":"eng","text":"Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally and it degrades the ECM for several weeks. Here, we provide two minimally invasive and transient protocols for microglia-enabled PNN disassembly in mouse cortex: repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes. For complete details on the use and execution of this protocol, please refer to Venturino et al. (2021)."}],"language":[{"iso":"eng"}],"date_published":"2021-12-17T00:00:00Z","ddc":["573"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2021","article_number":"101012","intvolume":"         2"},{"date_published":"2021-12-10T00:00:00Z","intvolume":"        23","year":"2021","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"has_accepted_license":"1","citation":{"ama":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. <i>Molecular Therapy - Methods and Clinical Development</i>. 2021;23:210-224. doi:<a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">10.1016/j.omtm.2021.09.006</a>","ista":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. 23, 210–224.","chicago":"Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” <i>Molecular Therapy - Methods and Clinical Development</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">https://doi.org/10.1016/j.omtm.2021.09.006</a>.","mla":"Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” <i>Molecular Therapy - Methods and Clinical Development</i>, vol. 23, Elsevier, 2021, pp. 210–24, doi:<a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">10.1016/j.omtm.2021.09.006</a>.","ieee":"M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert, “Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment,” <i>Molecular Therapy - Methods and Clinical Development</i>, vol. 23. Elsevier, pp. 210–224, 2021.","short":"M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular Therapy - Methods and Clinical Development 23 (2021) 210–224.","apa":"Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., &#38; Siegert, S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. <i>Molecular Therapy - Methods and Clinical Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">https://doi.org/10.1016/j.omtm.2021.09.006</a>"},"day":"10","_id":"10655","abstract":[{"text":"Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.\r\n","lang":"eng"}],"language":[{"iso":"eng"}],"external_id":{"isi":["000748748500019"]},"type":"journal_article","quality_controlled":"1","ec_funded":1,"scopus_import":"1","page":"210-224","status":"public","publication":"Molecular Therapy - Methods and Clinical Development","date_updated":"2025-04-14T07:41:46Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"isi":1,"file_date_updated":"2022-01-24T07:43:09Z","title":"Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment","date_created":"2022-01-23T23:01:28Z","oa_version":"Published Version","publication_identifier":{"eissn":["2329-0501"]},"file":[{"access_level":"open_access","file_size":4794147,"date_created":"2022-01-24T07:43:09Z","success":1,"content_type":"application/pdf","file_name":"2021_MolTherMethodsClinDev_Maes.pdf","checksum":"77dc540e8011c5475031bdf6ccef20a6","relation":"main_file","creator":"cchlebak","date_updated":"2022-01-24T07:43:09Z","file_id":"10657"}],"publication_status":"published","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"Yes","publisher":"Elsevier","volume":23,"author":[{"full_name":"Maes, Margaret E","last_name":"Maes","id":"3838F452-F248-11E8-B48F-1D18A9856A87","first_name":"Margaret E","orcid":"0000-0001-9642-1085"},{"full_name":"Wögenstein, Gabriele M.","last_name":"Wögenstein","first_name":"Gabriele M."},{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","orcid":"0000-0001-9434-8902","last_name":"Colombo","full_name":"Colombo, Gloria"},{"first_name":"Raquel","id":"15240fc1-dbcd-11ea-9d1d-ac5a786425fd","orcid":"0000-0001-8293-4568","last_name":"Casado Polanco","full_name":"Casado Polanco, Raquel"},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"article_type":"original","project":[{"name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715571"}],"month":"12","department":[{"_id":"SaSi"},{"_id":"SiHi"}],"acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 715571). The research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility, the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger and Michael Schunn for their animal colony management and support. We would also like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally, we would like to thank the Siegert team members for discussion about the manuscript.","oa":1,"doi":"10.1016/j.omtm.2021.09.006"},{"publication_status":"published","file":[{"file_id":"9693","date_updated":"2021-07-19T13:32:17Z","creator":"cziletti","relation":"main_file","checksum":"f056255f6d01fd9a86b5387635928173","file_name":"2021_CellReports_Venturino.pdf","content_type":"application/pdf","success":1,"file_size":56388540,"date_created":"2021-07-19T13:32:17Z","access_level":"open_access"}],"publication_identifier":{"eissn":["2211-1247"]},"oa_version":"Published Version","date_created":"2021-07-11T22:01:16Z","title":"Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain","oa":1,"doi":"10.1016/j.celrep.2021.109313","acknowledgement":"We thank the scientific service units at IST Austria, especially the IST bioimaging facility, the preclinical facility, and, specifically, Michael Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King, and all Siegert group members for constant feedback on the project and manuscript; Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination for OD plasticity experiments; and Ana Morello from MIT for technical assistance with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian Academy of Sciences at the Institute of Science and Technology Austria to R.S., from the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the European Research Council (grant 715571 to S.S.), and the National Eye Institute of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.) and R01EY023037 (diversity supplement to H.D.J-C.).","department":[{"_id":"SaSi"}],"month":"07","article_type":"original","project":[{"grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"},{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"name":"Microglia action towards neuronal circuit formation and function in health and disease","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571"}],"author":[{"full_name":"Venturino, Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","orcid":"0000-0003-2356-9403"},{"first_name":"Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5297-733X","full_name":"Schulz, Rouven","last_name":"Schulz"},{"full_name":"De Jesús-Cortés, Héctor","last_name":"De Jesús-Cortés","first_name":"Héctor"},{"orcid":"0000-0001-9642-1085","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","last_name":"Maes","full_name":"Maes, Margaret E"},{"full_name":"Nagy, Balint","last_name":"Nagy","id":"93C65ECC-A6F2-11E9-8DF9-9712E6697425","first_name":"Balint"},{"first_name":"Francis","last_name":"Reilly-Andújar","full_name":"Reilly-Andújar, Francis"},{"last_name":"Colombo","full_name":"Colombo, Gloria","orcid":"0000-0001-9434-8902","first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0002-1867","id":"850B2E12-9CD4-11E9-837F-E719E6697425","first_name":"Ryan J","last_name":"Cubero","full_name":"Cubero, Ryan J"},{"last_name":"Schoot Uiterkamp","full_name":"Schoot Uiterkamp, Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","first_name":"Florianne E"},{"first_name":"Mark F.","full_name":"Bear, Mark F.","last_name":"Bear"},{"full_name":"Siegert, Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","orcid":"0000-0001-8635-0877"}],"volume":36,"publisher":"Elsevier","article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/the-twinkle-and-the-brain/"}]},"pmid":1,"quality_controlled":"1","type":"journal_article","external_id":{"isi":["000670188500004"],"pmid":["34233180"]},"_id":"9642","abstract":[{"lang":"eng","text":"Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain."}],"language":[{"iso":"eng"}],"citation":{"ieee":"A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,” <i>Cell Reports</i>, vol. 36, no. 1. Elsevier, 2021.","short":"A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar, G. Colombo, R.J. Cubero, F.E. Miteva, M.F. Bear, S. Siegert, Cell Reports 36 (2021).","mla":"Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>.","apa":"Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar, F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>","ista":"Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar F, Colombo G, Cubero RJ, Miteva FE, Bear MF, Siegert S. 2021. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313.","ama":"Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. 2021;36(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>","chicago":"Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>."},"day":"06","has_accepted_license":"1","ddc":["570"],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","year":"2021","intvolume":"        36","article_number":"109313","date_published":"2021-07-06T00:00:00Z","file_date_updated":"2021-07-19T13:32:17Z","isi":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"publication":"Cell Reports","date_updated":"2026-04-03T09:46:05Z","status":"public","scopus_import":"1","ec_funded":1,"issue":"1"},{"status":"public","scopus_import":"1","ec_funded":1,"file_date_updated":"2020-07-14T12:47:33Z","isi":1,"date_updated":"2025-03-31T16:01:17Z","publication":"Neuroscience Letters","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","year":"2019","article_number":"134310","intvolume":"       707","date_published":"2019-08-10T00:00:00Z","quality_controlled":"1","type":"journal_article","external_id":{"isi":["000486094600037"],"pmid":["31158432"]},"language":[{"iso":"eng"}],"_id":"6521","abstract":[{"text":"Microglia have emerged as a critical component of neurodegenerative diseases. Genetic manipulation of microglia can elucidate their functional impact in disease. In neuroscience, recombinant viruses such as lentiviruses and adeno-associated viruses (AAVs) have been successfully used to target various cell types in the brain, although effective transduction of microglia is rare. In this review, we provide a short background of lentiviruses and AAVs, and strategies for designing recombinant viral vectors. Then, we will summarize recent literature on successful microglial transductions in vitro and in vivo, and discuss the current challenges. Finally, we provide guidelines for reporting the efficiency and specificity of viral targeting in microglia, which will enable the microglial research community to assess and improve methodologies for future studies.","lang":"eng"}],"citation":{"ista":"Maes ME, Colombo G, Schulz R, Siegert S. 2019. Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges. Neuroscience Letters. 707, 134310.","ama":"Maes ME, Colombo G, Schulz R, Siegert S. Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges. <i>Neuroscience Letters</i>. 2019;707. doi:<a href=\"https://doi.org/10.1016/j.neulet.2019.134310\">10.1016/j.neulet.2019.134310</a>","chicago":"Maes, Margaret E, Gloria Colombo, Rouven Schulz, and Sandra Siegert. “Targeting Microglia with Lentivirus and AAV: Recent Advances and Remaining Challenges.” <i>Neuroscience Letters</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.neulet.2019.134310\">https://doi.org/10.1016/j.neulet.2019.134310</a>.","ieee":"M. E. Maes, G. Colombo, R. Schulz, and S. Siegert, “Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges,” <i>Neuroscience Letters</i>, vol. 707. Elsevier, 2019.","short":"M.E. Maes, G. Colombo, R. Schulz, S. Siegert, Neuroscience Letters 707 (2019).","mla":"Maes, Margaret E., et al. “Targeting Microglia with Lentivirus and AAV: Recent Advances and Remaining Challenges.” <i>Neuroscience Letters</i>, vol. 707, 134310, Elsevier, 2019, doi:<a href=\"https://doi.org/10.1016/j.neulet.2019.134310\">10.1016/j.neulet.2019.134310</a>.","apa":"Maes, M. E., Colombo, G., Schulz, R., &#38; Siegert, S. (2019). Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges. <i>Neuroscience Letters</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neulet.2019.134310\">https://doi.org/10.1016/j.neulet.2019.134310</a>"},"day":"10","has_accepted_license":"1","publisher":"Elsevier","article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","pmid":1,"doi":"10.1016/j.neulet.2019.134310","oa":1,"month":"08","department":[{"_id":"SaSi"}],"project":[{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"},{"name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425"},{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"article_type":"original","author":[{"orcid":"0000-0001-9642-1085","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","full_name":"Maes, Margaret E","last_name":"Maes"},{"first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","last_name":"Colombo"},{"orcid":"0000-0001-5297-733X","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","first_name":"Rouven","full_name":"Schulz, Rouven","last_name":"Schulz"},{"orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","last_name":"Siegert"}],"volume":707,"publication_identifier":{"issn":["0304-3940"]},"oa_version":"Published Version","title":"Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges","date_created":"2019-06-05T13:16:24Z","publication_status":"published","file":[{"access_level":"open_access","date_created":"2019-06-08T11:44:20Z","file_size":1779287,"content_type":"application/pdf","file_name":"2019_Neuroscience_Maes.pdf","checksum":"553c9dbd39727fbed55ee991c51ca4d1","creator":"dernst","date_updated":"2020-07-14T12:47:33Z","file_id":"6551","relation":"main_file"}]},{"publication_identifier":{"issn":["2168-622X"]},"title":"How MicroRNAs Are involved in splitting the mind","date_created":"2018-12-11T11:50:58Z","oa_version":"Submitted Version","publication_status":"published","publist_id":"6074","file":[{"checksum":"649aee381f30f7ef7e9efa912d41c2e3","file_name":"IST-2018-981-v1+1_YNP150011_annotatedproof_FINAL.pdf","date_updated":"2020-07-14T12:44:41Z","creator":"system","relation":"main_file","file_id":"5278","access_level":"open_access","content_type":"application/pdf","date_created":"2018-12-12T10:17:24Z","file_size":601679}],"article_processing_charge":"No","publisher":"American Medical Association","pmid":1,"oa":1,"doi":"10.1001/jamapsychiatry.2015.3144","pubrep_id":"981","author":[{"first_name":"Lihuei","full_name":"Tsai, Lihuei","last_name":"Tsai"},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"volume":73,"month":"04","department":[{"_id":"SaSi"}],"intvolume":"        73","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","ddc":["576","610"],"year":"2016","date_published":"2016-04-01T00:00:00Z","external_id":{"isi":["000373444700017"],"pmid":["26963490"]},"abstract":[{"lang":"eng","text":"This article provides an introduction to the role of microRNAs in the nervous system and outlines their potential involvement in the pathophysiology of schizophrenia, which is hypothesized to arise owing to environmental factors and genetic predisposition."}],"_id":"1253","language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","day":"01","citation":{"chicago":"Tsai, Lihuei, and Sandra Siegert. “How MicroRNAs Are Involved in Splitting the Mind.” <i>JAMA Psychiatry</i>. American Medical Association, 2016. <a href=\"https://doi.org/10.1001/jamapsychiatry.2015.3144\">https://doi.org/10.1001/jamapsychiatry.2015.3144</a>.","ista":"Tsai L, Siegert S. 2016. How MicroRNAs Are involved in splitting the mind. JAMA Psychiatry. 73(4), 409–410.","ama":"Tsai L, Siegert S. How MicroRNAs Are involved in splitting the mind. <i>JAMA Psychiatry</i>. 2016;73(4):409-410. doi:<a href=\"https://doi.org/10.1001/jamapsychiatry.2015.3144\">10.1001/jamapsychiatry.2015.3144</a>","apa":"Tsai, L., &#38; Siegert, S. (2016). How MicroRNAs Are involved in splitting the mind. <i>JAMA Psychiatry</i>. American Medical Association. <a href=\"https://doi.org/10.1001/jamapsychiatry.2015.3144\">https://doi.org/10.1001/jamapsychiatry.2015.3144</a>","short":"L. Tsai, S. Siegert, JAMA Psychiatry 73 (2016) 409–410.","ieee":"L. Tsai and S. Siegert, “How MicroRNAs Are involved in splitting the mind,” <i>JAMA Psychiatry</i>, vol. 73, no. 4. American Medical Association, pp. 409–410, 2016.","mla":"Tsai, Lihuei, and Sandra Siegert. “How MicroRNAs Are Involved in Splitting the Mind.” <i>JAMA Psychiatry</i>, vol. 73, no. 4, American Medical Association, 2016, pp. 409–10, doi:<a href=\"https://doi.org/10.1001/jamapsychiatry.2015.3144\">10.1001/jamapsychiatry.2015.3144</a>."},"has_accepted_license":"1","page":"409 - 410","status":"public","issue":"4","scopus_import":"1","file_date_updated":"2020-07-14T12:44:41Z","publication":"JAMA Psychiatry","date_updated":"2025-09-22T09:08:34Z","isi":1},{"file_date_updated":"2020-07-14T12:45:07Z","isi":1,"date_updated":"2025-09-18T10:59:24Z","publication":"Molecular and Cellular Neuroscience","status":"public","page":"13 - 31","type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"_id":"1613","abstract":[{"lang":"eng","text":"In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells.\r\n\r\nIn this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD."}],"external_id":{"isi":["000376225300003"]},"has_accepted_license":"1","citation":{"chicago":"Mungenast, Alison, Sandra Siegert, and Li Tsai. “Modeling Alzheimer’s Disease with Human Induced Pluripotent Stem (IPS) Cells.” <i>Molecular and Cellular Neuroscience</i>. Academic Press, 2016. <a href=\"https://doi.org/doi:10.1016/j.mcn.2015.11.010\">https://doi.org/doi:10.1016/j.mcn.2015.11.010</a>.","ista":"Mungenast A, Siegert S, Tsai L. 2016. Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. 73, 13–31.","ama":"Mungenast A, Siegert S, Tsai L. Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells. <i>Molecular and Cellular Neuroscience</i>. 2016;73:13-31. doi:<a href=\"https://doi.org/doi:10.1016/j.mcn.2015.11.010\">doi:10.1016/j.mcn.2015.11.010</a>","apa":"Mungenast, A., Siegert, S., &#38; Tsai, L. (2016). Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells. <i>Molecular and Cellular Neuroscience</i>. Academic Press. <a href=\"https://doi.org/doi:10.1016/j.mcn.2015.11.010\">https://doi.org/doi:10.1016/j.mcn.2015.11.010</a>","short":"A. Mungenast, S. Siegert, L. Tsai, Molecular and Cellular Neuroscience 73 (2016) 13–31.","ieee":"A. Mungenast, S. Siegert, and L. Tsai, “Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells,” <i>Molecular and Cellular Neuroscience</i>, vol. 73. Academic Press, pp. 13–31, 2016.","mla":"Mungenast, Alison, et al. “Modeling Alzheimer’s Disease with Human Induced Pluripotent Stem (IPS) Cells.” <i>Molecular and Cellular Neuroscience</i>, vol. 73, Academic Press, 2016, pp. 13–31, doi:<a href=\"https://doi.org/doi:10.1016/j.mcn.2015.11.010\">doi:10.1016/j.mcn.2015.11.010</a>."},"day":"01","year":"2016","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","ddc":["616"],"intvolume":"        73","date_published":"2016-06-01T00:00:00Z","pubrep_id":"979","acknowledgement":"This work was supported by NIH grant R01-AG047661 to LHT. The art in Fig. 1 was created by Julian Wong.","doi":"doi:10.1016/j.mcn.2015.11.010","oa":1,"month":"06","volume":73,"author":[{"full_name":"Mungenast, Alison","last_name":"Mungenast","first_name":"Alison"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","last_name":"Siegert","full_name":"Siegert, Sandra"},{"first_name":"Li","full_name":"Tsai, Li","last_name":"Tsai"}],"publisher":"Academic Press","corr_author":"1","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_processing_charge":"No","extern":"1","publist_id":"5553","publication_status":"published","file":[{"access_level":"open_access","content_type":"application/pdf","file_size":632915,"date_created":"2018-12-12T10:12:50Z","checksum":"620254114e04d5d6e7f37d15e4b8ace4","file_name":"IST-2018-979-v1+1_Mungenast_2015_acceptedManuscript.pdf","relation":"main_file","creator":"system","date_updated":"2020-07-14T12:45:07Z","file_id":"4970"}],"oa_version":"Submitted Version","title":"Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells","date_created":"2018-12-11T11:53:02Z"},{"extern":1,"publisher":"Nature Publishing Group","page":"1008 - 1016","status":"public","publication":"Nature Neuroscience","date_updated":"2021-01-12T06:53:18Z","volume":18,"author":[{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Sandra Siegert","last_name":"Siegert"},{"full_name":"Seo, Jinsoo","last_name":"Seo","first_name":"Jinsoo"},{"first_name":"Ester","last_name":"Kwon","full_name":"Kwon, Ester J"},{"full_name":"Rudenko, Andrii","last_name":"Rudenko","first_name":"Andrii"},{"last_name":"Cho","full_name":"Cho, Sukhee","first_name":"Sukhee"},{"first_name":"Wenyuan","last_name":"Wang","full_name":"Wang, Wenyuan"},{"full_name":"Flood, Zachary C","last_name":"Flood","first_name":"Zachary"},{"last_name":"Martorell","full_name":"Martorell, Anthony J","first_name":"Anthony"},{"last_name":"Ericsson","full_name":"Ericsson, Maria","first_name":"Maria"},{"full_name":"Mungenast, Alison E","last_name":"Mungenast","first_name":"Alison"},{"last_name":"Tsai","full_name":"Tsai, Lihuei","first_name":"Lihuei"}],"month":"07","acknowledgement":"S.S. was supported by a Human Frontier Science Program (HFSP) long-term postdoctoral fellowship and a Swiss National Science Foundation fellowship for prospective researchers. E.J.K. was supported by a Simons Foundation Postdoctoral Fellowship. A.R. was supported by a NARSAD Young Investigator Award. This work was supported by a Seed Grant from the Simons Center for the Social Brain and US National Institutes of Health grant RO1 MH 091115 to L.-H.T.","doi":"10.1038/nn.4023","date_published":"2015-07-01T00:00:00Z","title":"The schizophrenia risk gene product miR-137 alters presynaptic plasticity","date_created":"2018-12-11T11:54:05Z","intvolume":"        18","year":"2015","day":"01","citation":{"mla":"Siegert, Sandra, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters Presynaptic Plasticity.” <i>Nature Neuroscience</i>, vol. 18, Nature Publishing Group, 2015, pp. 1008–16, doi:<a href=\"https://doi.org/10.1038/nn.4023\">10.1038/nn.4023</a>.","ieee":"S. Siegert <i>et al.</i>, “The schizophrenia risk gene product miR-137 alters presynaptic plasticity,” <i>Nature Neuroscience</i>, vol. 18. Nature Publishing Group, pp. 1008–1016, 2015.","short":"S. Siegert, J. Seo, E. Kwon, A. Rudenko, S. Cho, W. Wang, Z. Flood, A. Martorell, M. Ericsson, A. Mungenast, L. Tsai, Nature Neuroscience 18 (2015) 1008–1016.","apa":"Siegert, S., Seo, J., Kwon, E., Rudenko, A., Cho, S., Wang, W., … Tsai, L. (2015). The schizophrenia risk gene product miR-137 alters presynaptic plasticity. <i>Nature Neuroscience</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/nn.4023\">https://doi.org/10.1038/nn.4023</a>","ama":"Siegert S, Seo J, Kwon E, et al. The schizophrenia risk gene product miR-137 alters presynaptic plasticity. <i>Nature Neuroscience</i>. 2015;18:1008-1016. doi:<a href=\"https://doi.org/10.1038/nn.4023\">10.1038/nn.4023</a>","ista":"Siegert S, Seo J, Kwon E, Rudenko A, Cho S, Wang W, Flood Z, Martorell A, Ericsson M, Mungenast A, Tsai L. 2015. The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nature Neuroscience. 18, 1008–1016.","chicago":"Siegert, Sandra, Jinsoo Seo, Ester Kwon, Andrii Rudenko, Sukhee Cho, Wenyuan Wang, Zachary Flood, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters Presynaptic Plasticity.” <i>Nature Neuroscience</i>. Nature Publishing Group, 2015. <a href=\"https://doi.org/10.1038/nn.4023\">https://doi.org/10.1038/nn.4023</a>."},"abstract":[{"text":"Noncoding variants in the human MIR137 gene locus increase schizophrenia risk with genome-wide significance. However, the functional consequence of these risk alleles is unknown. Here we examined induced human neurons harboring the minor alleles of four disease-associated single nucleotide polymorphisms in MIR137. We observed increased MIR137 levels compared to those in major allele–carrying cells. microRNA-137 gain of function caused downregulation of the presynaptic target genes complexin-1 (Cplx1), Nsf and synaptotagmin-1 (Syt1), leading to impaired vesicle release. In vivo, miR-137 gain of function resulted in changes in synaptic vesicle pool distribution, impaired induction of mossy fiber long-term potentiation and deficits in hippocampus-dependent learning and memory. By sequestering endogenous miR-137, we were able to ameliorate the synaptic phenotypes. Moreover, reinstatement of Syt1 expression partially restored synaptic plasticity, demonstrating the importance of Syt1 as a miR-137 target. Our data provide new insight into the mechanism by which miR-137 dysregulation can impair synaptic plasticity in the hippocampus.","lang":"eng"}],"_id":"1802","publist_id":"5308","type":"journal_article","quality_controlled":0,"publication_status":"published"},{"extern":1,"issue":"23","status":"public","page":"7291 - 7296","publisher":"National Academy of Sciences","volume":112,"author":[{"last_name":"Rei","full_name":"Rei, Damien","first_name":"Damien"},{"first_name":"Xenos","full_name":"Mason, Xenos","last_name":"Mason"},{"full_name":"Seo, Jinsoo","last_name":"Seo","first_name":"Jinsoo"},{"first_name":"Johannes","full_name":"Gräff, Johannes","last_name":"Gräff"},{"first_name":"Andrii","last_name":"Rudenko","full_name":"Rudenko, Andrii"},{"first_name":"Jùn","full_name":"Wang, Jùn","last_name":"Wang"},{"first_name":"Richard","full_name":"Rueda, Richard","last_name":"Rueda"},{"full_name":"Sandra Siegert","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","orcid":"0000-0001-8635-0877"},{"first_name":"Sukhee","last_name":"Cho","full_name":"Cho, Sukhee"},{"last_name":"Canter","full_name":"Canter, Rebecca G","first_name":"Rebecca"},{"last_name":"Mungenast","full_name":"Mungenast, Alison E","first_name":"Alison"},{"first_name":"Karl","last_name":"Deisseroth","full_name":"Deisseroth, Karl A"},{"last_name":"Tsai","full_name":"Tsai, Lihuei","first_name":"Lihuei"}],"publication":"PNAS","date_updated":"2021-01-12T06:53:18Z","month":"06","doi":"10.1073/pnas.1415845112","acknowledgement":"AG047661; NIH; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung\nNS051874; NIH; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung\nSNSF; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung","date_created":"2018-12-11T11:54:06Z","title":"Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway","date_published":"2015-06-09T00:00:00Z","intvolume":"       112","year":"2015","citation":{"mla":"Rei, Damien, et al. “Basolateral Amygdala Bidirectionally Modulates Stress Induced Hippocampal Learning and Memory Deficits through a P25/Cdk5-Dependent Pathway.” <i>PNAS</i>, vol. 112, no. 23, National Academy of Sciences, 2015, pp. 7291–96, doi:<a href=\"https://doi.org/10.1073/pnas.1415845112\">10.1073/pnas.1415845112</a>.","short":"D. Rei, X. Mason, J. Seo, J. Gräff, A. Rudenko, J. Wang, R. Rueda, S. Siegert, S. Cho, R. Canter, A. Mungenast, K. Deisseroth, L. Tsai, PNAS 112 (2015) 7291–7296.","ieee":"D. Rei <i>et al.</i>, “Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway,” <i>PNAS</i>, vol. 112, no. 23. National Academy of Sciences, pp. 7291–7296, 2015.","apa":"Rei, D., Mason, X., Seo, J., Gräff, J., Rudenko, A., Wang, J., … Tsai, L. (2015). Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway. <i>PNAS</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1415845112\">https://doi.org/10.1073/pnas.1415845112</a>","ama":"Rei D, Mason X, Seo J, et al. Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway. <i>PNAS</i>. 2015;112(23):7291-7296. doi:<a href=\"https://doi.org/10.1073/pnas.1415845112\">10.1073/pnas.1415845112</a>","ista":"Rei D, Mason X, Seo J, Gräff J, Rudenko A, Wang J, Rueda R, Siegert S, Cho S, Canter R, Mungenast A, Deisseroth K, Tsai L. 2015. Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway. PNAS. 112(23), 7291–7296.","chicago":"Rei, Damien, Xenos Mason, Jinsoo Seo, Johannes Gräff, Andrii Rudenko, Jùn Wang, Richard Rueda, et al. “Basolateral Amygdala Bidirectionally Modulates Stress Induced Hippocampal Learning and Memory Deficits through a P25/Cdk5-Dependent Pathway.” <i>PNAS</i>. National Academy of Sciences, 2015. <a href=\"https://doi.org/10.1073/pnas.1415845112\">https://doi.org/10.1073/pnas.1415845112</a>."},"day":"09","_id":"1803","abstract":[{"text":"Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memoryrelated genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.","lang":"eng"}],"publication_status":"published","quality_controlled":0,"type":"journal_article","publist_id":"5307"},{"day":"01","citation":{"ista":"Siegert S, Cabuy E, Scherf B, Kohler H, Panda S, Le Y, Fehling H, Gaidatzis D, Stadler M, Roska B. 2012. Transcriptional code and disease map for adult retinal cell types. Nature Neuroscience. 15(3), 487–495.","ama":"Siegert S, Cabuy E, Scherf B, et al. Transcriptional code and disease map for adult retinal cell types. <i>Nature Neuroscience</i>. 2012;15(3):487-495. doi:<a href=\"https://doi.org/10.1038/nn.3032\">10.1038/nn.3032</a>","chicago":"Siegert, Sandra, Erik Cabuy, Brigitte Scherf, Hubertus Kohler, Satchidananda Panda, Yunzheng Le, Hans Fehling, Dimos Gaidatzis, Michael Stadler, and Botond Roska. “Transcriptional Code and Disease Map for Adult Retinal Cell Types.” <i>Nature Neuroscience</i>. Nature Publishing Group, 2012. <a href=\"https://doi.org/10.1038/nn.3032\">https://doi.org/10.1038/nn.3032</a>.","ieee":"S. Siegert <i>et al.</i>, “Transcriptional code and disease map for adult retinal cell types,” <i>Nature Neuroscience</i>, vol. 15, no. 3. Nature Publishing Group, pp. 487–495, 2012.","short":"S. Siegert, E. Cabuy, B. Scherf, H. Kohler, S. Panda, Y. Le, H. Fehling, D. Gaidatzis, M. Stadler, B. Roska, Nature Neuroscience 15 (2012) 487–495.","mla":"Siegert, Sandra, et al. “Transcriptional Code and Disease Map for Adult Retinal Cell Types.” <i>Nature Neuroscience</i>, vol. 15, no. 3, Nature Publishing Group, 2012, pp. 487–95, doi:<a href=\"https://doi.org/10.1038/nn.3032\">10.1038/nn.3032</a>.","apa":"Siegert, S., Cabuy, E., Scherf, B., Kohler, H., Panda, S., Le, Y., … Roska, B. (2012). Transcriptional code and disease map for adult retinal cell types. <i>Nature Neuroscience</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/nn.3032\">https://doi.org/10.1038/nn.3032</a>"},"type":"journal_article","publist_id":"5309","publication_status":"published","quality_controlled":0,"abstract":[{"text":"Brain circuits are assembled from a large variety of morphologically and functionally diverse cell types. It is not known how the intermingled cell types of an individual adult brain region differ in their expressed genomes. Here we describe an atlas of cell type transcriptomes in one brain region, the mouse retina. We found that each adult cell type expressed a specific set of genes, including a unique set of transcription factors, forming a 'barcode' for cell identity. Cell type transcriptomes carried enough information to categorize cells into morphological classes and types. Several genes that were specifically expressed in particular retinal circuit elements, such as inhibitory neuron types, are associated with eye diseases. The resource described here allows gene expression to be compared across adult retinal cell types, experimenting with specific transcription factors to differentiate stem or somatic cells to retinal cell types, and predicting cellular targets of newly discovered disease-associated genes.","lang":"eng"}],"_id":"1801","date_published":"2012-03-01T00:00:00Z","date_created":"2018-12-11T11:54:05Z","title":"Transcriptional code and disease map for adult retinal cell types","year":"2012","intvolume":"        15","month":"03","publication":"Nature Neuroscience","date_updated":"2021-01-12T06:53:17Z","author":[{"orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Sandra Siegert","last_name":"Siegert"},{"first_name":"Erik","full_name":"Cabuy, Erik","last_name":"Cabuy"},{"full_name":"Scherf, Brigitte G","last_name":"Scherf","first_name":"Brigitte"},{"full_name":"Kohler, Hubertus","last_name":"Kohler","first_name":"Hubertus"},{"first_name":"Satchidananda","full_name":"Panda, Satchidananda","last_name":"Panda"},{"first_name":"Yunzheng","full_name":"Le, Yunzheng","last_name":"Le"},{"first_name":"Hans","last_name":"Fehling","full_name":"Fehling, Hans J"},{"last_name":"Gaidatzis","full_name":"Gaidatzis, Dimos","first_name":"Dimos"},{"first_name":"Michael","full_name":"Stadler, Michael B","last_name":"Stadler"},{"first_name":"Botond","full_name":"Roska, Botond M","last_name":"Roska"}],"volume":15,"acknowledgement":"The study was supported by Friedrich Miescher Institute funds, Alcon award, a National Center of Competence in Research Genetics grant, a European Research Council grant, a Swiss-Hungarian grant, and RETICIRC, TREATRUSH, SEEBETTER and OPTONEURO grants from the European Union to B.R.","doi":"10.1038/nn.3032","issue":"3","extern":1,"publisher":"Nature Publishing Group","status":"public","page":"487 - 495"},{"_id":"1800","abstract":[{"text":"Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.","lang":"eng"}],"quality_controlled":0,"publication_status":"published","publist_id":"5310","type":"journal_article","day":"23","citation":{"ista":"Busskamp V, Duebel J, Bálya D, Fradot M, Viney T, Siegert S, Groner A, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Pâques M, Mohand Saïd S, Trono D, Deisseroth K, Sähel J, Picaud S, Roska B. 2010. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 329(5990), 413–417.","ama":"Busskamp V, Duebel J, Bálya D, et al. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. <i>Science</i>. 2010;329(5990):413-417. doi:<a href=\"https://doi.org/10.1126/science.1190897\">10.1126/science.1190897</a>","chicago":"Busskamp, Volker, Jens Duebel, Dávid Bálya, Mathias Fradot, Tim Viney, Sandra Siegert, Anna Groner, et al. “Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa.” <i>Science</i>. American Association for the Advancement of Science, 2010. <a href=\"https://doi.org/10.1126/science.1190897\">https://doi.org/10.1126/science.1190897</a>.","ieee":"V. Busskamp <i>et al.</i>, “Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa,” <i>Science</i>, vol. 329, no. 5990. American Association for the Advancement of Science, pp. 413–417, 2010.","short":"V. Busskamp, J. Duebel, D. Bálya, M. Fradot, T. Viney, S. Siegert, A. Groner, E. Cabuy, V. Forster, M. Seeliger, M. Biel, P. Humphries, M. Pâques, S. Mohand Saïd, D. Trono, K. Deisseroth, J. Sähel, S. Picaud, B. Roska, Science 329 (2010) 413–417.","mla":"Busskamp, Volker, et al. “Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa.” <i>Science</i>, vol. 329, no. 5990, American Association for the Advancement of Science, 2010, pp. 413–17, doi:<a href=\"https://doi.org/10.1126/science.1190897\">10.1126/science.1190897</a>.","apa":"Busskamp, V., Duebel, J., Bálya, D., Fradot, M., Viney, T., Siegert, S., … Roska, B. (2010). Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.1190897\">https://doi.org/10.1126/science.1190897</a>"},"intvolume":"       329","year":"2010","date_created":"2018-12-11T11:54:05Z","title":"Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa","date_published":"2010-07-23T00:00:00Z","doi":"10.1126/science.1190897","acknowledgement":"This study was supported by Friedrich Miescher Institute funds; a U.S. Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant; a Marie Curie Excellence grant and a European Union (EU) HEALTH-F2-223156 grant to B.R.; a grant from the EU (RETICIRC) to B.R. and S.P.; grants from the Agence nationale de la recherche (MEDINAS, RETINE) to S.P.; a Center Grant from Foundation Fighting Blindness (U.S.) to S.M.-S. and J.A.S.; grants from the Swiss National Science Foundation and the EU to D.T.; a grant from the EU (TREATRUSH) to J.A.S., S.P., and B.R.; a Marie Curie Postdoctoral Fellowship to D.B.; and a National Centers of Competence in Research Frontiers in Genetics fellowship to V.B. and A.C.G. The Ocular Genetics Unit at Trinity College Dublin is supported by Science Foundation Ireland","volume":329,"author":[{"first_name":"Volker","full_name":"Busskamp, Volker","last_name":"Busskamp"},{"full_name":"Duebel, Jens","last_name":"Duebel","first_name":"Jens"},{"first_name":"Dávid","last_name":"Bálya","full_name":"Bálya, Dávid"},{"last_name":"Fradot","full_name":"Fradot, Mathias","first_name":"Mathias"},{"first_name":"Tim","full_name":"Viney, Tim J","last_name":"Viney"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert","full_name":"Sandra Siegert"},{"first_name":"Anna","last_name":"Groner","full_name":"Groner, Anna C"},{"last_name":"Cabuy","full_name":"Cabuy, Erik","first_name":"Erik"},{"last_name":"Forster","full_name":"Forster, Valérie","first_name":"Valérie"},{"first_name":"Mathias","last_name":"Seeliger","full_name":"Seeliger, Mathias W"},{"full_name":"Biel, Martin","last_name":"Biel","first_name":"Martin"},{"first_name":"Peter","last_name":"Humphries","full_name":"Humphries, Peter"},{"first_name":"Michel","last_name":"Pâques","full_name":"Pâques, Michel"},{"last_name":"Mohand Saïd","full_name":"Mohand-Saïd, Saddek","first_name":"Saddek"},{"first_name":"Didier","full_name":"Trono, Didier","last_name":"Trono"},{"first_name":"Karl","last_name":"Deisseroth","full_name":"Deisseroth, Karl A"},{"last_name":"Sähel","full_name":"Sähel, José A","first_name":"José"},{"last_name":"Picaud","full_name":"Picaud, Serge A","first_name":"Serge"},{"first_name":"Botond","last_name":"Roska","full_name":"Roska, Botond M"}],"date_updated":"2021-01-12T06:53:17Z","publication":"Science","month":"07","status":"public","page":"413 - 417","publisher":"American Association for the Advancement of Science","extern":1,"issue":"5990"},{"acknowledgement":"This study was supported by Friedrich Miescher Institute funds, a US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant, a Marie Curie Excellence grant, a National Center for Competence in Research in Genetics grant and a European Union HEALTH-F2-223156 grant to B.R., and by National Institute of Neurological Disorders and Stroke contracts N01NS02331 and HHSN271200723701C to N.H.","doi":"10.1038/nn.2370","publication":"Nature Neuroscience","date_updated":"2021-01-12T06:53:16Z","author":[{"full_name":"Sandra Siegert","last_name":"Siegert","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra"},{"full_name":"Scherf, Brigitte G","last_name":"Scherf","first_name":"Brigitte"},{"first_name":"Karina","full_name":"Del Punta, Karina","last_name":"Del Punta"},{"first_name":"Nick","full_name":"Didkovsky, Nick","last_name":"Didkovsky"},{"full_name":"Heintz, Nathaniel M","last_name":"Heintz","first_name":"Nathaniel"},{"last_name":"Roska","full_name":"Roska, Botond M","first_name":"Botond"}],"volume":12,"month":"09","publisher":"Nature Publishing Group","page":"1197 - 1204","status":"public","issue":"9","extern":1,"abstract":[{"text":"The mammalian brain is assembled from thousands of neuronal cell types that are organized in distinct circuits to perform behaviorally relevant computations. Transgenic mouse lines with selectively marked cell types would facilitate our ability to dissect functional components of complex circuits. We carried out a screen for cell type-specific green fluorescent protein expression in the retina using BAC transgenic mice from the GENSAT project. Among others, we identified mouse lines in which the inhibitory cell types of the night vision and directional selective circuit were selectively labeled. We quantified the stratification patterns to predict potential synaptic connectivity between marked cells of different lines and found that some of the lines enabled targeted recordings and imaging of cell types from developing or mature retinal circuits. Our results suggest the potential use of a stratification-based screening approach for characterizing neuronal circuitry in other layered brain structures, such as the neocortex.","lang":"eng"}],"_id":"1798","type":"journal_article","publist_id":"5312","publication_status":"published","quality_controlled":0,"citation":{"ista":"Siegert S, Scherf B, Del Punta K, Didkovsky N, Heintz N, Roska B. 2009. Genetic address book for retinal cell types. Nature Neuroscience. 12(9), 1197–1204.","ama":"Siegert S, Scherf B, Del Punta K, Didkovsky N, Heintz N, Roska B. Genetic address book for retinal cell types. <i>Nature Neuroscience</i>. 2009;12(9):1197-1204. doi:<a href=\"https://doi.org/10.1038/nn.2370\">10.1038/nn.2370</a>","chicago":"Siegert, Sandra, Brigitte Scherf, Karina Del Punta, Nick Didkovsky, Nathaniel Heintz, and Botond Roska. “Genetic Address Book for Retinal Cell Types.” <i>Nature Neuroscience</i>. Nature Publishing Group, 2009. <a href=\"https://doi.org/10.1038/nn.2370\">https://doi.org/10.1038/nn.2370</a>.","short":"S. Siegert, B. Scherf, K. Del Punta, N. Didkovsky, N. Heintz, B. Roska, Nature Neuroscience 12 (2009) 1197–1204.","ieee":"S. Siegert, B. Scherf, K. Del Punta, N. Didkovsky, N. Heintz, and B. Roska, “Genetic address book for retinal cell types,” <i>Nature Neuroscience</i>, vol. 12, no. 9. Nature Publishing Group, pp. 1197–1204, 2009.","mla":"Siegert, Sandra, et al. “Genetic Address Book for Retinal Cell Types.” <i>Nature Neuroscience</i>, vol. 12, no. 9, Nature Publishing Group, 2009, pp. 1197–204, doi:<a href=\"https://doi.org/10.1038/nn.2370\">10.1038/nn.2370</a>.","apa":"Siegert, S., Scherf, B., Del Punta, K., Didkovsky, N., Heintz, N., &#38; Roska, B. (2009). Genetic address book for retinal cell types. <i>Nature Neuroscience</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/nn.2370\">https://doi.org/10.1038/nn.2370</a>"},"day":"01","intvolume":"        12","year":"2009","date_published":"2009-09-01T00:00:00Z","title":"Genetic address book for retinal cell types","date_created":"2018-12-11T11:54:04Z"}]