[{"volume":26,"type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2023-11-07T08:53:21Z","language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","doi":"10.1016/j.isci.2023.107780","date_published":"2023-10-20T00:00:00Z","intvolume":"        26","ddc":["570"],"scopus_import":"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.","department":[{"_id":"SaSi"}],"publisher":"Elsevier","month":"10","isi":1,"author":[{"orcid":"0000-0001-9642-1085","id":"3838F452-F248-11E8-B48F-1D18A9856A87","full_name":"Maes, Margaret E","last_name":"Maes","first_name":"Margaret E"},{"last_name":"Colombo","first_name":"Gloria","orcid":"0000-0001-9434-8902","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","full_name":"Colombo, Gloria"},{"first_name":"Florianne E","last_name":"Schoot Uiterkamp","full_name":"Schoot Uiterkamp, Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sternberg, Felix","last_name":"Sternberg","first_name":"Felix"},{"orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino","first_name":"Alessandro"},{"full_name":"Pohl, Elena E.","first_name":"Elena E.","last_name":"Pohl"},{"first_name":"Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"}],"date_updated":"2023-12-13T12:27:30Z","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>","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>","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.","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>.","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>.","short":"M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino, E.E. Pohl, S. Siegert, IScience 26 (2023)."},"publication":"iScience","publication_identifier":{"eissn":["2589-0042"]},"oa":1,"day":"20","title":"Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout","external_id":{"pmid":["37731609"],"isi":["001080403500001"]},"issue":"10","article_number":"107780","has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"year":"2023","_id":"14363","date_created":"2023-09-24T22:01:11Z","pmid":1,"file":[{"content_type":"application/pdf","file_size":8197935,"checksum":"be1a560efdd96d20712311f4fc54aac2","creator":"dernst","access_level":"open_access","success":1,"relation":"main_file","date_created":"2023-11-07T08:53:21Z","file_id":"14497","file_name":"2023_iScience_Maes.pdf","date_updated":"2023-11-07T08:53:21Z"}],"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"}],"publication_status":"published","article_type":"original","oa_version":"Published Version","article_processing_charge":"Yes","quality_controlled":"1"},{"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"language":[{"iso":"eng"}],"date_published":"2022-08-15T00:00:00Z","doi":"10.1038/s41467-022-32390-1","intvolume":"        13","ddc":["570"],"volume":13,"type":"journal_article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file_date_updated":"2022-08-29T06:44:30Z","month":"08","publisher":"Springer Nature","department":[{"_id":"SaSi"}],"isi":1,"scopus_import":"1","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.","title":"Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses","external_id":{"pmid":["35970889"],"isi":["000840984400032"]},"project":[{"_id":"267F75D8-B435-11E9-9278-68D0E5697425","name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling"}],"article_number":"4728","has_accepted_license":"1","author":[{"first_name":"Rouven","last_name":"Schulz","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven","orcid":"0000-0001-5297-733X"},{"orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","full_name":"Korkut, Medina","last_name":"Korkut","first_name":"Medina"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","first_name":"Alessandro","last_name":"Venturino"},{"first_name":"Gloria","last_name":"Colombo","full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902"},{"first_name":"Sandra","last_name":"Siegert","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"citation":{"short":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022).","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>","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.","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>","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>.","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.","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>."},"date_updated":"2024-02-21T12:34:51Z","oa":1,"publication":"Nature Communications","publication_identifier":{"eissn":["2041-1723"]},"day":"15","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"}],"file":[{"access_level":"open_access","creator":"cchlebak","content_type":"application/pdf","file_size":7317396,"checksum":"191d9db0266e14a28d3a56dc7f65da84","date_updated":"2022-08-29T06:44:30Z","file_id":"12002","date_created":"2022-08-29T06:44:30Z","success":1,"relation":"main_file","file_name":"2022_NatComm_Schulz.pdf"}],"related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/dreaddful-mimicry/","description":"News on ISTA website"}],"record":[{"relation":"part_of_dissertation","id":"11945","status":"public"},{"id":"11542","status":"public","relation":"research_data"}]},"article_type":"original","publication_status":"published","article_processing_charge":"No","oa_version":"Published Version","quality_controlled":"1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"_id":"11995","year":"2022","date_created":"2022-08-28T22:01:59Z","pmid":1},{"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"year":"2022","_id":"12244","ec_funded":1,"pmid":1,"date_created":"2023-01-16T09:53:07Z","file":[{"file_name":"2022_NatureNeuroscience_Colombo.pdf","file_id":"12437","date_created":"2023-01-30T08:06:56Z","success":1,"relation":"main_file","date_updated":"2023-01-30T08:06:56Z","checksum":"28431146873096f52e0107b534f178c9","file_size":23789835,"content_type":"application/pdf","access_level":"open_access","creator":"dernst"}],"abstract":[{"lang":"eng","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."}],"article_type":"original","related_material":{"record":[{"status":"public","id":"12378","relation":"dissertation_contains"}],"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/","relation":"press_release"}]},"publication_status":"published","oa_version":"Published Version","keyword":["General Neuroscience"],"article_processing_charge":"No","quality_controlled":"1","citation":{"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.","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>.","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.","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>","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>","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."},"date_updated":"2024-03-25T23:30:10Z","author":[{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","full_name":"Colombo, Gloria","orcid":"0000-0001-9434-8902","first_name":"Gloria","last_name":"Colombo"},{"full_name":"Cubero, Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425","orcid":"0000-0003-0002-1867","first_name":"Ryan J","last_name":"Cubero"},{"full_name":"Kanari, Lida","first_name":"Lida","last_name":"Kanari"},{"last_name":"Venturino","first_name":"Alessandro","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schulz","first_name":"Rouven","full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5297-733X"},{"last_name":"Scolamiero","first_name":"Martina","full_name":"Scolamiero, Martina"},{"last_name":"Agerberg","first_name":"Jens","full_name":"Agerberg, Jens"},{"last_name":"Mathys","first_name":"Hansruedi","full_name":"Mathys, Hansruedi"},{"last_name":"Tsai","first_name":"Li-Huei","full_name":"Tsai, Li-Huei"},{"first_name":"Wojciech","last_name":"Chachólski","full_name":"Chachólski, Wojciech"},{"full_name":"Hess, Kathryn","last_name":"Hess","first_name":"Kathryn"},{"full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert"}],"publication":"Nature Neuroscience","publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"oa":1,"day":"01","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships"},{"_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715571","name":"Microglia action towards neuronal circuit formation and function in health and disease"}],"external_id":{"isi":["000862214700001"],"pmid":["36180790"]},"title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","issue":"10","has_accepted_license":"1","page":"1379-1393","scopus_import":"1","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.","department":[{"_id":"SaSi"}],"publisher":"Springer Nature","month":"10","isi":1,"volume":25,"type":"journal_article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file_date_updated":"2023-01-30T08:06:56Z","language":[{"iso":"eng"}],"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"doi":"10.1038/s41593-022-01167-6","date_published":"2022-10-01T00:00:00Z","intvolume":"        25","ddc":["570"]},{"ddc":["570"],"alternative_title":["ISTA Thesis"],"doi":"10.15479/at:ista:12378","date_published":"2022-11-11T00:00:00Z","language":[{"iso":"eng"}],"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"file_date_updated":"2023-04-12T22:30:03Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"dissertation","degree_awarded":"PhD","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"month":"11","page":"142","has_accepted_license":"1","project":[{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"}],"title":"MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes","day":"11","publication_identifier":{"issn":["2663-337X"]},"oa":1,"date_updated":"2023-08-04T09:40:37Z","citation":{"short":"G. Colombo, MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes, Institute of Science and Technology Austria, 2022.","ista":"Colombo G. 2022. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. Institute of Science and Technology Austria.","chicago":"Colombo, Gloria. “MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>.","apa":"Colombo, G. (2022). <i>MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12378\">https://doi.org/10.15479/at:ista:12378</a>","ieee":"G. Colombo, “MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes,” Institute of Science and Technology Austria, 2022.","ama":"Colombo G. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>","mla":"Colombo, Gloria. <i>MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12378\">10.15479/at:ista:12378</a>."},"author":[{"full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","first_name":"Gloria","last_name":"Colombo"}],"supervisor":[{"full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert"}],"oa_version":"Published Version","article_processing_charge":"No","publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","id":"12244","status":"public"}]},"file":[{"access_level":"closed","creator":"cchlebak","checksum":"8cd3ddfe9b53381dcf086023d8d8893a","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":23890382,"date_updated":"2023-04-12T22:30:03Z","file_name":"Gloria_Colombo_Thesis.docx","embargo_to":"open_access","file_id":"12379","date_created":"2023-01-25T14:31:32Z","relation":"source_file"},{"embargo":"2023-04-11","date_updated":"2023-04-12T22:30:03Z","file_id":"12380","date_created":"2023-01-25T14:31:36Z","relation":"main_file","file_name":"Gloria_Colombo_Thesis.pdf","access_level":"open_access","creator":"cchlebak","content_type":"application/pdf","file_size":13802421,"checksum":"8af4319c18b516e8758e9a6cb02b103b"}],"abstract":[{"text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to \r\ncharacterize these changes usually involve user-selected morphometric features, which \r\npreclude the identification of a spectrum of context-dependent morphological phenotypes. \r\nHere, we develop MorphOMICs, a topological data analysis approach, which enables semi\u0002automatic mapping of microglial morphology into an atlas of cue-dependent phenotypes,\r\novercomes feature-selection bias and minimizes biological variability. \r\nFirst, with MorphOMICs we derive the morphological spectrum of microglia across seven \r\nbrain regions during postnatal development and in two distinct Alzheimer’s disease \r\ndegeneration mouse models. We uncover region-specific and sexually dimorphic\r\nmorphological trajectories, with females showing an earlier morphological shift than males in \r\nthe degenerating brain. Overall, we demonstrate that both long primary- and short terminal \r\nprocesses provide distinct insights to morphological phenotypes. Moreover, using machine \r\nlearning to map novel condition on the spectrum, we observe that microglia morphologies \r\nreflect a dose-dependent adaptation upon ketamine anesthesia and do not recover to control \r\nmorphologies.\r\nNext, we took advantage of MorphOMICs to build a high-resolution and layer-specific map of \r\nmicroglial morphological spectrum in the retina, covering postnatal development and rd10 \r\ndegeneration. Here, following photoreceptor death, microglia assume an early development\u0002like morphology. Finally, we map microglial morphology following optic nerve crush on the \r\nretinal spectrum and observe a layer- and sex-dependent response. \r\nOverall, MorphOMICs opens a new perspective to analyze microglial morphology across \r\nmultiple conditions, and provides a novel tool to characterize microglial morphology beyond \r\nthe traditionally dichotomized view of microglia.","lang":"eng"}],"ec_funded":1,"date_created":"2023-01-25T14:27:43Z","year":"2022","_id":"12378","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}]},{"type":"journal_article","volume":23,"file_date_updated":"2022-01-24T07:43:09Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","doi":"10.1016/j.omtm.2021.09.006","date_published":"2021-12-10T00:00:00Z","language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","intvolume":"        23","ddc":["570"],"page":"210-224","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.","scopus_import":"1","publisher":"Elsevier","department":[{"_id":"SaSi"},{"_id":"SiHi"}],"month":"12","isi":1,"date_updated":"2023-11-16T13:12:03Z","author":[{"orcid":"0000-0001-9642-1085","full_name":"Maes, Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","last_name":"Maes","first_name":"Margaret E"},{"full_name":"Wögenstein, Gabriele M.","first_name":"Gabriele M.","last_name":"Wögenstein"},{"orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","last_name":"Colombo","first_name":"Gloria"},{"full_name":"Casado Polanco, Raquel","id":"15240fc1-dbcd-11ea-9d1d-ac5a786425fd","orcid":"0000-0001-8293-4568","first_name":"Raquel","last_name":"Casado Polanco"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert","first_name":"Sandra"}],"citation":{"short":"M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular Therapy - Methods and Clinical Development 23 (2021) 210–224.","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>.","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>","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.","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>","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>."},"day":"10","publication_identifier":{"eissn":["2329-0501"]},"publication":"Molecular Therapy - Methods and Clinical Development","oa":1,"project":[{"grant_number":"715571","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease"}],"external_id":{"isi":["000748748500019"]},"title":"Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment","has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ec_funded":1,"date_created":"2022-01-23T23:01:28Z","year":"2021","_id":"10655","article_type":"original","publication_status":"published","file":[{"creator":"cchlebak","access_level":"open_access","checksum":"77dc540e8011c5475031bdf6ccef20a6","file_size":4794147,"content_type":"application/pdf","date_updated":"2022-01-24T07:43:09Z","file_name":"2021_MolTherMethodsClinDev_Maes.pdf","relation":"main_file","date_created":"2022-01-24T07:43:09Z","success":1,"file_id":"10657"}],"abstract":[{"lang":"eng","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"}],"quality_controlled":"1","oa_version":"Published Version","article_processing_charge":"Yes"},{"title":"Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain","external_id":{"pmid":["34233180"],"isi":["000670188500004"]},"project":[{"name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"name":"Microglia action towards neuronal circuit formation and function in health and disease","call_identifier":"H2020","grant_number":"715571","_id":"25D4A630-B435-11E9-9278-68D0E5697425"}],"has_accepted_license":"1","issue":"1","article_number":"109313","citation":{"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, Schoot Uiterkamp 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.","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>.","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>","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.","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>","short":"A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar, G. Colombo, R.J. Cubero, F.E. Schoot Uiterkamp, M.F. Bear, S. Siegert, Cell Reports 36 (2021)."},"author":[{"first_name":"Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro"},{"orcid":"0000-0001-5297-733X","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven","first_name":"Rouven","last_name":"Schulz"},{"last_name":"De Jesús-Cortés","first_name":"Héctor","full_name":"De Jesús-Cortés, Héctor"},{"full_name":"Maes, Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9642-1085","last_name":"Maes","first_name":"Margaret E"},{"id":"93C65ECC-A6F2-11E9-8DF9-9712E6697425","full_name":"Nagy, Balint","first_name":"Balint","last_name":"Nagy"},{"last_name":"Reilly-Andújar","first_name":"Francis","full_name":"Reilly-Andújar, Francis"},{"last_name":"Colombo","first_name":"Gloria","orcid":"0000-0001-9434-8902","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","full_name":"Colombo, Gloria"},{"orcid":"0000-0003-0002-1867","full_name":"Cubero, Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425","last_name":"Cubero","first_name":"Ryan J"},{"first_name":"Florianne E","last_name":"Schoot Uiterkamp","id":"3526230C-F248-11E8-B48F-1D18A9856A87","full_name":"Schoot Uiterkamp, Florianne E"},{"full_name":"Bear, Mark F.","first_name":"Mark F.","last_name":"Bear"},{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-08-10T14:09:39Z","day":"06","oa":1,"publication_identifier":{"eissn":["22111247"]},"publication":"Cell Reports","publication_status":"published","related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/the-twinkle-and-the-brain/"}]},"article_type":"original","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":[{"date_created":"2021-07-19T13:32:17Z","success":1,"relation":"main_file","file_id":"9693","file_name":"2021_CellReports_Venturino.pdf","date_updated":"2021-07-19T13:32:17Z","file_size":56388540,"content_type":"application/pdf","checksum":"f056255f6d01fd9a86b5387635928173","creator":"cziletti","access_level":"open_access"}],"quality_controlled":"1","article_processing_charge":"No","oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"date_created":"2021-07-11T22:01:16Z","pmid":1,"ec_funded":1,"_id":"9642","year":"2021","date_published":"2021-07-06T00:00:00Z","doi":"10.1016/j.celrep.2021.109313","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","language":[{"iso":"eng"}],"ddc":["570"],"intvolume":"        36","type":"journal_article","volume":36,"file_date_updated":"2021-07-19T13:32:17Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"07","department":[{"_id":"SaSi"}],"publisher":"Elsevier","isi":1,"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.).","scopus_import":"1"},{"file_date_updated":"2020-07-14T12:47:33Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","type":"journal_article","volume":707,"ddc":["570"],"intvolume":"       707","date_published":"2019-08-10T00:00:00Z","doi":"10.1016/j.neulet.2019.134310","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"language":[{"iso":"eng"}],"scopus_import":"1","isi":1,"month":"08","publisher":"Elsevier","department":[{"_id":"SaSi"}],"day":"10","oa":1,"publication":"Neuroscience Letters","publication_identifier":{"issn":["0304-3940"]},"citation":{"short":"M.E. Maes, G. Colombo, R. Schulz, S. Siegert, Neuroscience Letters 707 (2019).","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>","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>","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.","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>.","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.","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>."},"date_updated":"2023-08-28T09:30:57Z","author":[{"orcid":"0000-0001-9642-1085","full_name":"Maes, Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","first_name":"Margaret E","last_name":"Maes"},{"first_name":"Gloria","last_name":"Colombo","orcid":"0000-0001-9434-8902","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","full_name":"Colombo, Gloria"},{"orcid":"0000-0001-5297-733X","full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","first_name":"Rouven","last_name":"Schulz"},{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"}],"has_accepted_license":"1","article_number":"134310","external_id":{"isi":["000486094600037"],"pmid":["31158432"]},"title":"Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges","project":[{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"},{"name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571","call_identifier":"H2020"},{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"pmid":1,"ec_funded":1,"date_created":"2019-06-05T13:16:24Z","_id":"6521","year":"2019","quality_controlled":"1","article_processing_charge":"No","oa_version":"Published Version","publication_status":"published","article_type":"original","abstract":[{"lang":"eng","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."}],"file":[{"file_name":"2019_Neuroscience_Maes.pdf","file_id":"6551","date_created":"2019-06-08T11:44:20Z","relation":"main_file","date_updated":"2020-07-14T12:47:33Z","checksum":"553c9dbd39727fbed55ee991c51ca4d1","file_size":1779287,"content_type":"application/pdf","access_level":"open_access","creator":"dernst"}]}]