[{"article_number":"49","year":"2025","publication_identifier":{"issn":["1552-5783"]},"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. ","doi":"10.1167/iovs.66.3.49","license":"https://creativecommons.org/licenses/by/4.0/","date_created":"2025-04-15T13:40:35Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"project":[{"_id":"7be82147-9f16-11ee-852c-f44682d73140","grant_number":"P37131","name":"Dissecting the morpho-functional relationship of microglia"},{"call_identifier":"FWF","name":"FWF Open Access Fund","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1"}],"type":"journal_article","title":"Optic nerve crush does not induce retinal ganglion cell loss in the contralateral eye","article_type":"original","DOAJ_listed":"1","publication_status":"published","APC_amount":"2236,02 EUR","day":"01","author":[{"id":"3526230C-F248-11E8-B48F-1D18A9856A87","first_name":"Florianne E","last_name":"Schoot Uiterkamp","full_name":"Schoot Uiterkamp, Florianne E"},{"last_name":"Maes","full_name":"Maes, Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","first_name":"Margaret E","orcid":"0000-0001-9642-1085"},{"last_name":"Alamalhoda","full_name":"Alamalhoda, Mohammad","first_name":"Mohammad"},{"first_name":"Arsalan","full_name":"Firoozi, Arsalan","last_name":"Firoozi"},{"orcid":"0000-0001-9434-8902","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","last_name":"Colombo","full_name":"Colombo, Gloria"},{"full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"issue":"3","oa_version":"Published Version","pmid":1,"abstract":[{"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.","lang":"eng"}],"file":[{"success":1,"date_created":"2025-04-15T13:49:10Z","content_type":"application/pdf","file_size":2721477,"creator":"dernst","date_updated":"2025-04-15T13:49:10Z","file_name":"2025_IOVS_SchootUiterkamp.pdf","file_id":"19567","relation":"main_file","access_level":"open_access","checksum":"e8722ce5792f6c08fe1e191f7de6f147"}],"external_id":{"pmid":["40126507"]},"date_published":"2025-03-01T00:00:00Z","publication":"Investigative Ophthalmology & Visual Science","date_updated":"2026-05-20T06:37:12Z","oa":1,"related_material":{"record":[{"id":"20467","relation":"dissertation_contains","status":"public"}],"link":[{"relation":"software","url":"https://github.com/siegert-lab/RGC-Quant"}]},"ddc":["570"],"file_date_updated":"2025-04-15T13:49:10Z","department":[{"_id":"SaSi"}],"scopus_import":"1","corr_author":"1","_id":"19566","status":"public","article_processing_charge":"Yes","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"has_accepted_license":"1","citation":{"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>","short":"F.E. Miteva, M.E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, S. Siegert, Investigative Ophthalmology &#38; Visual Science 66 (2025).","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.","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>.","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>"},"OA_type":"gold","volume":66,"quality_controlled":"1","publisher":"Association for Research in Vision and Ophthalmology","intvolume":"        66","OA_place":"publisher","month":"03"},{"supervisor":[{"orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","month":"10","OA_place":"publisher","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_processing_charge":"No","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"},{"_id":"PreCl"},{"_id":"LifeSc"}],"page":"99","citation":{"apa":"Miteva, F. E. (2025). <i>The role of cyclooxygenase 1 on microglial response to inflammatory stressors</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20467\">https://doi.org/10.15479/AT-ISTA-20467</a>","mla":"Miteva, Florianne E. <i>The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory Stressors</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20467\">10.15479/AT-ISTA-20467</a>.","ista":"Miteva FE. 2025. The role of cyclooxygenase 1 on microglial response to inflammatory stressors. Institute of Science and Technology Austria.","short":"F.E. Miteva, The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory Stressors, Institute of Science and Technology Austria, 2025.","chicago":"Miteva, Florianne E. “The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory Stressors.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20467\">https://doi.org/10.15479/AT-ISTA-20467</a>.","ama":"Miteva FE. The role of cyclooxygenase 1 on microglial response to inflammatory stressors. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20467\">10.15479/AT-ISTA-20467</a>","ieee":"F. E. Miteva, “The role of cyclooxygenase 1 on microglial response to inflammatory stressors,” Institute of Science and Technology Austria, 2025."},"has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"file_date_updated":"2025-10-23T11:33:06Z","ddc":["570"],"degree_awarded":"PhD","corr_author":"1","_id":"20467","status":"public","date_updated":"2026-05-20T06:37:12Z","related_material":{"record":[{"id":"19566","status":"public","relation":"part_of_dissertation"}]},"file":[{"date_updated":"2025-10-17T11:13:25Z","creator":"fschootu","file_size":13668588,"date_created":"2025-10-17T11:09:11Z","content_type":"application/pdf","checksum":"03537697be8c688d3a05cf948288e48f","embargo_to":"open_access","relation":"main_file","access_level":"closed","embargo":"2026-10-14","file_id":"20484","file_name":"2025_Miteva_Florianne_thesis.pdf"},{"file_size":28991918,"date_created":"2025-10-23T11:33:06Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2025-10-23T11:33:06Z","creator":"fschootu","relation":"source_file","access_level":"closed","file_id":"20525","file_name":"2025_Miteva_florianne_thesis.docx","checksum":"df4930d7211cf9cfe1254b77204dc1d3"}],"date_published":"2025-10-14T00:00:00Z","day":"14","author":[{"first_name":"Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","full_name":"Miteva, Florianne E","last_name":"Miteva"}],"oa_version":"Published Version","language":[{"iso":"eng"}],"type":"dissertation","title":"The role of cyclooxygenase 1 on microglial response to inflammatory stressors","project":[{"_id":"7be82147-9f16-11ee-852c-f44682d73140","grant_number":"P37131","name":"Dissecting the morpho-functional relationship of microglia"}],"publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"year":"2025","acknowledgement":"The work presented in this Thesis was carried out at the Institute of Science and Technology\r\nAustria (ISTA), and was supported by the Austrian Science Fund (FWF) [10.55776/P37131].\r\nI would like to thank the Scientific Service Units (SSU) of ISTA for the provided resources,\r\nspecifically the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF), and the\r\nPre-Clinical Facility (PCF) team, specifically Sonja Haslinger, Claudia Gold, and Michael\r\nSchunn, for mouse colony management and support. ","doi":"10.15479/AT-ISTA-20467","alternative_title":["ISTA Thesis"],"date_created":"2025-10-14T10:24:41Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd"},{"status":"public","_id":"14363","corr_author":"1","scopus_import":"1","file_date_updated":"2023-11-07T08:53:21Z","department":[{"_id":"SaSi"}],"ddc":["570"],"oa":1,"date_updated":"2024-10-09T21:07:01Z","month":"10","intvolume":"        26","publisher":"Elsevier","volume":26,"quality_controlled":"1","citation":{"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>","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>.","short":"M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino, E.E. Pohl, S. Siegert, IScience 26 (2023).","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.","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>","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>.","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."},"has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_processing_charge":"Yes","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"publication_status":"published","article_type":"original","type":"journal_article","title":"Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout","isi":1,"language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2023-09-24T22:01:11Z","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","article_number":"107780","year":"2023","publication_identifier":{"eissn":["2589-0042"]},"publication":"iScience","external_id":{"isi":["001080403500001"],"pmid":["37731609"]},"file":[{"success":1,"date_created":"2023-11-07T08:53:21Z","content_type":"application/pdf","file_size":8197935,"creator":"dernst","date_updated":"2023-11-07T08:53:21Z","file_name":"2023_iScience_Maes.pdf","file_id":"14497","access_level":"open_access","relation":"main_file","checksum":"be1a560efdd96d20712311f4fc54aac2"}],"date_published":"2023-10-20T00:00:00Z","abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"issue":"10","author":[{"full_name":"Maes, Margaret E","last_name":"Maes","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9642-1085"},{"first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","full_name":"Colombo, Gloria","last_name":"Colombo","orcid":"0000-0001-9434-8902"},{"full_name":"Schoot Uiterkamp, Florianne E","last_name":"Schoot Uiterkamp","first_name":"Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Felix","full_name":"Sternberg, Felix","last_name":"Sternberg"},{"orcid":"0000-0003-2356-9403","last_name":"Venturino","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro"},{"full_name":"Pohl, Elena E.","last_name":"Pohl","first_name":"Elena E."},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877"}],"day":"20"},{"publisher":"Elsevier","intvolume":"        36","month":"07","article_processing_charge":"No","ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"has_accepted_license":"1","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.","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>.","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.","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).","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>","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>."},"volume":36,"quality_controlled":"1","ddc":["570"],"department":[{"_id":"SaSi"}],"file_date_updated":"2021-07-19T13:32:17Z","scopus_import":"1","_id":"9642","status":"public","date_updated":"2026-04-03T09:46:05Z","related_material":{"link":[{"url":"https://ist.ac.at/en/news/the-twinkle-and-the-brain/","description":"News on IST Homepage","relation":"press_release"}]},"oa":1,"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."}],"file":[{"checksum":"f056255f6d01fd9a86b5387635928173","file_id":"9693","file_name":"2021_CellReports_Venturino.pdf","relation":"main_file","access_level":"open_access","creator":"cziletti","date_updated":"2021-07-19T13:32:17Z","date_created":"2021-07-19T13:32:17Z","content_type":"application/pdf","success":1,"file_size":56388540}],"external_id":{"pmid":["34233180"],"isi":["000670188500004"]},"date_published":"2021-07-06T00:00:00Z","publication":"Cell Reports","day":"06","author":[{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino"},{"orcid":"0000-0001-5297-733X","full_name":"Schulz, Rouven","last_name":"Schulz","first_name":"Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Héctor","full_name":"De Jesús-Cortés, Héctor","last_name":"De Jesús-Cortés"},{"orcid":"0000-0001-9642-1085","full_name":"Maes, Margaret E","last_name":"Maes","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Balint","id":"93C65ECC-A6F2-11E9-8DF9-9712E6697425","full_name":"Nagy, Balint","last_name":"Nagy"},{"first_name":"Francis","last_name":"Reilly-Andújar","full_name":"Reilly-Andújar, Francis"},{"last_name":"Colombo","full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","orcid":"0000-0001-9434-8902"},{"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"},{"last_name":"Bear","full_name":"Bear, Mark F.","first_name":"Mark F."},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"issue":"1","pmid":1,"oa_version":"Published Version","language":[{"iso":"eng"}],"isi":1,"project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571"}],"title":"Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain","type":"journal_article","article_type":"original","publication_status":"published","publication_identifier":{"eissn":["2211-1247"]},"year":"2021","article_number":"109313","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.).","date_created":"2021-07-11T22:01:16Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd"},{"scopus_import":"1","department":[{"_id":"SaSi"}],"status":"public","_id":"7880","date_updated":"2025-07-10T11:54:48Z","oa":1,"intvolume":"       295","publisher":"ASBMB Publications","month":"04","page":"5229-5244","article_processing_charge":"No","volume":295,"quality_controlled":"1","citation":{"apa":"Fagan, R. R., Kearney, P. J., Sweeney, C. G., Luethi, D., Schoot Uiterkamp, F. E., Schicker, K., … Melikian, H. E. (2020). Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. <i>Journal of Biological Chemistry</i>. ASBMB Publications. <a href=\"https://doi.org/10.1074/jbc.RA120.012628\">https://doi.org/10.1074/jbc.RA120.012628</a>","mla":"Fagan, Rita R., et al. “Dopamine Transporter Trafficking and Rit2 GTPase: Mechanism of Action and in Vivo Impact.” <i>Journal of Biological Chemistry</i>, vol. 295, no. 16, ASBMB Publications, 2020, pp. 5229–44, doi:<a href=\"https://doi.org/10.1074/jbc.RA120.012628\">10.1074/jbc.RA120.012628</a>.","short":"R.R. Fagan, P.J. Kearney, C.G. Sweeney, D. Luethi, F.E. Schoot Uiterkamp, K. Schicker, B.S. Alejandro, L.C. O’Connor, H.H. Sitte, H.E. Melikian, Journal of Biological Chemistry 295 (2020) 5229–5244.","ista":"Fagan RR, Kearney PJ, Sweeney CG, Luethi D, Schoot Uiterkamp FE, Schicker K, Alejandro BS, O’Connor LC, Sitte HH, Melikian HE. 2020. Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. Journal of Biological Chemistry. 295(16), 5229–5244.","chicago":"Fagan, Rita R., Patrick J. Kearney, Carolyn G. Sweeney, Dino Luethi, Florianne E Schoot Uiterkamp, Klaus Schicker, Brian S. Alejandro, Lauren C. O’Connor, Harald H. Sitte, and Haley E. Melikian. “Dopamine Transporter Trafficking and Rit2 GTPase: Mechanism of Action and in Vivo Impact.” <i>Journal of Biological Chemistry</i>. ASBMB Publications, 2020. <a href=\"https://doi.org/10.1074/jbc.RA120.012628\">https://doi.org/10.1074/jbc.RA120.012628</a>.","ama":"Fagan RR, Kearney PJ, Sweeney CG, et al. Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. <i>Journal of Biological Chemistry</i>. 2020;295(16):5229-5244. doi:<a href=\"https://doi.org/10.1074/jbc.RA120.012628\">10.1074/jbc.RA120.012628</a>","ieee":"R. R. Fagan <i>et al.</i>, “Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact,” <i>Journal of Biological Chemistry</i>, vol. 295, no. 16. ASBMB Publications, pp. 5229–5244, 2020."},"type":"journal_article","title":"Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact","isi":1,"language":[{"iso":"eng"}],"publication_status":"published","article_type":"original","doi":"10.1074/jbc.RA120.012628","publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"year":"2020","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2020-05-24T22:00:59Z","abstract":[{"text":"Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals. ","lang":"eng"}],"publication":"Journal of Biological Chemistry","external_id":{"pmid":["32132171"],"isi":["000530288000006"]},"date_published":"2020-04-17T00:00:00Z","author":[{"first_name":"Rita R.","full_name":"Fagan, Rita R.","last_name":"Fagan"},{"last_name":"Kearney","full_name":"Kearney, Patrick J.","first_name":"Patrick J."},{"first_name":"Carolyn G.","last_name":"Sweeney","full_name":"Sweeney, Carolyn G."},{"first_name":"Dino","last_name":"Luethi","full_name":"Luethi, Dino"},{"first_name":"Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","full_name":"Schoot Uiterkamp, Florianne E","last_name":"Schoot Uiterkamp"},{"full_name":"Schicker, Klaus","last_name":"Schicker","first_name":"Klaus"},{"first_name":"Brian S.","last_name":"Alejandro","full_name":"Alejandro, Brian S."},{"first_name":"Lauren C.","full_name":"O'Connor, Lauren C.","last_name":"O'Connor"},{"first_name":"Harald H.","last_name":"Sitte","full_name":"Sitte, Harald H."},{"last_name":"Melikian","full_name":"Melikian, Haley E.","first_name":"Haley E."}],"day":"17","pmid":1,"oa_version":"Submitted Version","issue":"16","main_file_link":[{"open_access":"1","url":"https://escholarship.umassmed.edu/oapubs/4187"}]}]