[{"title":"Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses)","file":[{"creator":"rschulz","access_level":"open_access","relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_name":"Source Data.xlsx","file_size":135784571,"date_created":"2022-07-08T10:56:52Z","file_id":"11543","checksum":"71e8186583f3adbb6c69a88ac9e6e49b","date_updated":"2022-07-08T10:56:52Z","success":1}],"related_material":{"link":[{"relation":"contains","url":"https://www.biorxiv.org/content/10.1101/2021.06.21.449162v1"}],"record":[{"id":"11995","status":"public","relation":"used_in_publication"}]},"has_accepted_license":"1","file_date_updated":"2022-07-08T10:56:52Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"citation":{"chicago":"Schulz, Rouven. “Source Data (Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses).” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/AT:ISTA:11542\">https://doi.org/10.15479/AT:ISTA:11542</a>.","ieee":"R. Schulz, “Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses).” Institute of Science and Technology Austria, 2022.","apa":"Schulz, R. (2022). Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses). Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:11542\">https://doi.org/10.15479/AT:ISTA:11542</a>","short":"R. Schulz, (2022).","mla":"Schulz, Rouven. <i>Source Data (Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses)</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:11542\">10.15479/AT:ISTA:11542</a>.","ista":"Schulz R. 2022. Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses), Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:11542\">10.15479/AT:ISTA:11542</a>.","ama":"Schulz R. Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses). 2022. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:11542\">10.15479/AT:ISTA:11542</a>"},"date_created":"2022-07-08T11:03:02Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"oa_version":"None","date_published":"2022-01-01T00:00:00Z","_id":"11542","oa":1,"contributor":[{"first_name":"Sandra","contributor_type":"contact_person","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"author":[{"first_name":"Rouven","full_name":"Schulz, Rouven","orcid":"0000-0001-5297-733X","last_name":"Schulz","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"}],"type":"research_data","status":"public","year":"2022","publisher":"Institute of Science and Technology Austria","date_updated":"2024-02-21T12:34:51Z","doi":"10.15479/AT:ISTA:11542"},{"citation":{"chicago":"Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>.","ieee":"R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function,” Institute of Science and Technology Austria, 2022.","apa":"Schulz, R. (2022). <i>Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>","ista":"Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria.","short":"R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022.","mla":"Schulz, Rouven. <i>Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>.","ama":"Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>"},"project":[{"_id":"267F75D8-B435-11E9-9278-68D0E5697425","name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling"}],"has_accepted_license":"1","alternative_title":["ISTA Thesis"],"file":[{"access_level":"open_access","content_type":"application/pdf","relation":"main_file","creator":"rschulz","date_created":"2022-08-25T08:59:57Z","file_id":"11970","checksum":"61b1b666a210ff7cdd0e95ea75207a13","success":1,"date_updated":"2022-08-25T08:59:57Z","file_name":"Thesis_Rouven_Schulz_2022_final.pdf","file_size":28079331},{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","creator":"rschulz","date_updated":"2022-08-25T09:33:31Z","checksum":"2b8f95ea1c134dbdb927b41b1dbeeeb5","date_created":"2022-08-25T09:00:11Z","file_id":"11971","file_size":27226963,"file_name":"Thesis_Rouven_Schulz_2022_final.docx"}],"title":"Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function","related_material":{"record":[{"relation":"dissertation_contains","id":"11995","status":"public"}]},"date_updated":"2023-08-03T13:02:26Z","status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"degree_awarded":"PhD","abstract":[{"text":"G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level.","lang":"eng"}],"day":"23","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"oa_version":"Published Version","publication_status":"published","page":"133","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"date_created":"2022-08-23T11:33:11Z","file_date_updated":"2022-08-25T09:33:31Z","article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","ddc":["570"],"publication_identifier":{"issn":["2663-337X"]},"month":"08","supervisor":[{"last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","first_name":"Sandra"}],"year":"2022","publisher":"Institute of Science and Technology Austria","doi":"10.15479/at:ista:11945","language":[{"iso":"eng"}],"type":"dissertation","_id":"11945","oa":1,"author":[{"orcid":"0000-0001-5297-733X","last_name":"Schulz","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven","first_name":"Rouven"}],"date_published":"2022-08-23T00:00:00Z"},{"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","ddc":["570"],"file_date_updated":"2022-08-29T06:44:30Z","intvolume":"        13","date_created":"2022-08-28T22:01:59Z","article_number":"4728","pmid":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.","department":[{"_id":"SaSi"}],"isi":1,"volume":13,"article_type":"original","month":"08","quality_controlled":"1","publication_identifier":{"eissn":["2041-1723"]},"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1038/s41467-022-32390-1","publisher":"Springer Nature","year":"2022","date_published":"2022-08-15T00:00:00Z","author":[{"id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","last_name":"Schulz","orcid":"0000-0001-5297-733X","first_name":"Rouven","full_name":"Schulz, Rouven"},{"first_name":"Medina","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","last_name":"Korkut"},{"first_name":"Alessandro","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Colombo","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","first_name":"Gloria"},{"full_name":"Siegert, Sandra","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert"}],"oa":1,"_id":"11995","scopus_import":"1","has_accepted_license":"1","project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"citation":{"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.","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>","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>.","short":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022).","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.","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>"},"publication":"Nature Communications","external_id":{"pmid":["35970889"],"isi":["000840984400032"]},"related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/dreaddful-mimicry/"}],"record":[{"relation":"part_of_dissertation","id":"11945","status":"public"},{"relation":"research_data","status":"public","id":"11542"}]},"title":"Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses","file":[{"date_created":"2022-08-29T06:44:30Z","file_id":"12002","checksum":"191d9db0266e14a28d3a56dc7f65da84","success":1,"date_updated":"2022-08-29T06:44:30Z","file_name":"2022_NatComm_Schulz.pdf","file_size":7317396,"access_level":"open_access","content_type":"application/pdf","relation":"main_file","creator":"cchlebak"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"status":"public","date_updated":"2024-02-21T12:34:51Z","oa_version":"Published Version","publication_status":"published","day":"15","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","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."}]},{"issue":"10","scopus_import":"1","has_accepted_license":"1","project":[{"call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"grant_number":"715571","call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425"}],"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.","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>.","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.","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>","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."},"publication":"Nature Neuroscience","external_id":{"pmid":["36180790"],"isi":["000862214700001"]},"related_material":{"record":[{"relation":"dissertation_contains","id":"12378","status":"public"}],"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/"}]},"file":[{"creator":"dernst","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_size":23789835,"file_name":"2022_NatureNeuroscience_Colombo.pdf","date_updated":"2023-01-30T08:06:56Z","success":1,"file_id":"12437","date_created":"2023-01-30T08:06:56Z","checksum":"28431146873096f52e0107b534f178c9"}],"title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"status":"public","date_updated":"2024-03-25T23:30:10Z","oa_version":"Published Version","publication_status":"published","page":"1379-1393","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"01","ec_funded":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"}],"article_processing_charge":"No","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file_date_updated":"2023-01-30T08:06:56Z","keyword":["General Neuroscience"],"intvolume":"        25","date_created":"2023-01-16T09:53:07Z","pmid":1,"department":[{"_id":"SaSi"}],"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.","isi":1,"volume":25,"article_type":"original","month":"10","quality_controlled":"1","publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1038/s41593-022-01167-6","publisher":"Springer Nature","year":"2022","date_published":"2022-10-01T00:00:00Z","author":[{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","last_name":"Colombo","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","first_name":"Gloria"},{"id":"850B2E12-9CD4-11E9-837F-E719E6697425","last_name":"Cubero","orcid":"0000-0003-0002-1867","first_name":"Ryan J","full_name":"Cubero, Ryan J"},{"first_name":"Lida","full_name":"Kanari, Lida","last_name":"Kanari"},{"full_name":"Venturino, Alessandro","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","orcid":"0000-0003-2356-9403"},{"first_name":"Rouven","full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","last_name":"Schulz","orcid":"0000-0001-5297-733X"},{"last_name":"Scolamiero","first_name":"Martina","full_name":"Scolamiero, Martina"},{"full_name":"Agerberg, Jens","first_name":"Jens","last_name":"Agerberg"},{"first_name":"Hansruedi","full_name":"Mathys, Hansruedi","last_name":"Mathys"},{"full_name":"Tsai, Li-Huei","first_name":"Li-Huei","last_name":"Tsai"},{"first_name":"Wojciech","full_name":"Chachólski, Wojciech","last_name":"Chachólski"},{"last_name":"Hess","full_name":"Hess, Kathryn","first_name":"Kathryn"},{"orcid":"0000-0001-8635-0877","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","full_name":"Siegert, Sandra"}],"oa":1,"_id":"12244"},{"publication":"Cell Reports","file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","creator":"cziletti","checksum":"f056255f6d01fd9a86b5387635928173","file_id":"9693","date_created":"2021-07-19T13:32:17Z","date_updated":"2021-07-19T13:32:17Z","success":1,"file_name":"2021_CellReports_Venturino.pdf","file_size":56388540}],"title":"Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/the-twinkle-and-the-brain/"}]},"external_id":{"isi":["000670188500004"],"pmid":["34233180"]},"scopus_import":"1","issue":"1","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.","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>.","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>","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).","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>.","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>"},"project":[{"grant_number":"665385","call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"715571","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425"}],"day":"06","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"oa_version":"Published Version","publication_status":"published","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."}],"ec_funded":1,"status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"date_updated":"2023-08-10T14:09:39Z","isi":1,"volume":36,"article_type":"original","month":"07","publication_identifier":{"eissn":["22111247"]},"quality_controlled":"1","file_date_updated":"2021-07-19T13:32:17Z","article_processing_charge":"No","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":"        36","article_number":"109313","date_created":"2021-07-11T22:01:16Z","department":[{"_id":"SaSi"}],"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.).","pmid":1,"date_published":"2021-07-06T00:00:00Z","author":[{"full_name":"Venturino, Alessandro","first_name":"Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","last_name":"Schulz","orcid":"0000-0001-5297-733X","full_name":"Schulz, Rouven","first_name":"Rouven"},{"last_name":"De Jesús-Cortés","full_name":"De Jesús-Cortés, Héctor","first_name":"Héctor"},{"orcid":"0000-0001-9642-1085","last_name":"Maes","id":"3838F452-F248-11E8-B48F-1D18A9856A87","first_name":"Margaret E","full_name":"Maes, Margaret E"},{"last_name":"Nagy","id":"93C65ECC-A6F2-11E9-8DF9-9712E6697425","full_name":"Nagy, Balint","first_name":"Balint"},{"last_name":"Reilly-Andújar","first_name":"Francis","full_name":"Reilly-Andújar, Francis"},{"first_name":"Gloria","full_name":"Colombo, Gloria","last_name":"Colombo","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902"},{"first_name":"Ryan J","full_name":"Cubero, Ryan J","orcid":"0000-0003-0002-1867","last_name":"Cubero","id":"850B2E12-9CD4-11E9-837F-E719E6697425"},{"full_name":"Schoot Uiterkamp, Florianne E","first_name":"Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","last_name":"Schoot Uiterkamp"},{"full_name":"Bear, Mark F.","first_name":"Mark F.","last_name":"Bear"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","orcid":"0000-0001-8635-0877","first_name":"Sandra","full_name":"Siegert, Sandra"}],"_id":"9642","oa":1,"type":"journal_article","doi":"10.1016/j.celrep.2021.109313","language":[{"iso":"eng"}],"year":"2021","publisher":"Elsevier"},{"publication_status":"published","oa_version":"Published Version","day":"10","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"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"}],"date_updated":"2023-08-28T09:30:57Z","status":"public","publication":"Neuroscience Letters","external_id":{"isi":["000486094600037"],"pmid":["31158432"]},"file":[{"date_updated":"2020-07-14T12:47:33Z","date_created":"2019-06-08T11:44:20Z","file_id":"6551","checksum":"553c9dbd39727fbed55ee991c51ca4d1","file_size":1779287,"file_name":"2019_Neuroscience_Maes.pdf","content_type":"application/pdf","relation":"main_file","access_level":"open_access","creator":"dernst"}],"title":"Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges","project":[{"call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"grant_number":"715571","call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425"},{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"citation":{"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>","short":"M.E. Maes, G. Colombo, R. Schulz, S. Siegert, Neuroscience Letters 707 (2019).","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."},"scopus_import":"1","has_accepted_license":"1","author":[{"orcid":"0000-0001-9642-1085","id":"3838F452-F248-11E8-B48F-1D18A9856A87","last_name":"Maes","first_name":"Margaret E","full_name":"Maes, Margaret E"},{"last_name":"Colombo","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","first_name":"Gloria","full_name":"Colombo, Gloria"},{"first_name":"Rouven","full_name":"Schulz, Rouven","last_name":"Schulz","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5297-733X"},{"full_name":"Siegert, Sandra","first_name":"Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"}],"oa":1,"_id":"6521","date_published":"2019-08-10T00:00:00Z","language":[{"iso":"eng"}],"doi":"10.1016/j.neulet.2019.134310","publisher":"Elsevier","year":"2019","type":"journal_article","month":"08","quality_controlled":"1","publication_identifier":{"issn":["0304-3940"]},"isi":1,"article_type":"original","volume":707,"article_number":"134310","date_created":"2019-06-05T13:16:24Z","pmid":1,"department":[{"_id":"SaSi"}],"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"file_date_updated":"2020-07-14T12:47:33Z","intvolume":"       707"}]