{"doi":"10.1016/j.immuni.2021.10.006","title":"Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring","abstract":null,"journal":"Immunity","year":2021,"id":632306,"datarank":0.7485648880168105,"base_score":4.990432586778736,"endowment":4.990432586778736,"self_citation_contribution":0.7485648880168105,"citation_network_contribution":0.0,"self_endowment_contribution":0.7485648880168105,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":146,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1638966,"name":"Genni Desiato","orcid":"0000-0001-5281-0097","position":1,"is_corresponding":false},{"id":811521,"name":"Sara Mancinelli","orcid":"0000-0002-6290-5425","position":2,"is_corresponding":false},{"id":1638970,"name":"Giuliana Fossati","orcid":"0000-0003-0321-3936","position":3,"is_corresponding":false},{"id":1638972,"name":"Marco Rasile","orcid":null,"position":4,"is_corresponding":false},{"id":228562,"name":"Raffaella Morini","orcid":"0000-0002-4403-6932","position":5,"is_corresponding":false},{"id":555753,"name":"Marija Markicevic","orcid":"0000-0003-0983-432X","position":6,"is_corresponding":false},{"id":1638978,"name":"Christina Grimm","orcid":null,"position":7,"is_corresponding":false},{"id":1638979,"name":"Clara Amegandjin","orcid":null,"position":8,"is_corresponding":false},{"id":1638980,"name":"Alberto Termanini","orcid":"0000-0002-9697-906X","position":9,"is_corresponding":false},{"id":1228455,"name":"Clelia Peano","orcid":"0000-0001-7055-3629","position":10,"is_corresponding":false},{"id":630742,"name":"Paolo Kunderfranco","orcid":"0000-0001-7477-8710","position":11,"is_corresponding":false},{"id":1638981,"name":"Graziella di Cristo","orcid":null,"position":12,"is_corresponding":false},{"id":555752,"name":"Valerio Zerbi","orcid":"0000-0001-7984-9565","position":13,"is_corresponding":false},{"id":1638982,"name":"Elisabetta Menna","orcid":"0000-0003-2062-0154","position":14,"is_corresponding":false},{"id":11088,"name":"Simona Lodato","orcid":"0000-0001-6498-2590","position":15,"is_corresponding":false},{"id":228574,"name":"Michela Matteoli","orcid":"0000-0002-3569-7843","position":16,"is_corresponding":false},{"id":555754,"name":"Davide Pozzi","orcid":"0000-0001-6436-0556","position":17,"is_corresponding":false},{"id":1638962,"name":"Filippo Mirabella","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring","abstract":"Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 elevation via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led to overall brain hyperconnectivity in offspring into adulthood. IL-6 activated synaptogenesis gene programs in glutamatergic neurons and required the transcription factor STAT3 and expression of the RGS4 gene. The STAT3-RGS4 pathway was also activated in neonatal brains during poly(I:C)-induced maternal immune activation, which mimics viral infection during pregnancy. These findings indicate that IL-6 elevation at early developmental stages is sufficient to exert a long-lasting effect on glutamatergic synaptogenesis and brain connectivity, providing a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders.","is_dataset_classified":null,"base_score":4.990432586778736,"endowment":4.990432586778736,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34758338","pmcid":"PMC8585508","openalex_id":"https://openalex.org/W3207129859","authors":[],"funders":[{"funder_name":"Fondazione Cariplo","grant_id":"2019-1785","title":null},{"funder_name":"Fondazione Cariplo","grant_id":"2017-0622","title":null},{"funder_name":"Ministero della Salute","grant_id":"RF2018-12365280","title":null},{"funder_name":"Ministero dell’Istruzione, dell’Università e della Ricerca","grant_id":"FISM 2019/R-Single/032","title":null},{"funder_name":"Ministero dell’Istruzione, dell’Università e della Ricerca","grant_id":"2017A9MK4R","title":null},{"funder_name":"Fondazione Telethon","grant_id":"GGP19226A","title":null},{"funder_name":"Ministero dell'Istruzione dell'Università e della Ricerca","grant_id":"unidentified","title":"unidentified"},{"funder_name":"FISM","grant_id":"","title":null},{"funder_name":"Fondazione Antonio Carlo Monzino","grant_id":"","title":null},{"funder_name":"Ferring Pharmaceuticals","grant_id":"","title":null},{"funder_name":"Fondazione Cassa di Risparmio di Pisa","grant_id":"","title":null},{"funder_name":"Università degli Studi di Torino","grant_id":"","title":null}],"total_grants":12,"fwci":7.9451,"citation_percentile":0.98258298,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":19},{"year":2023,"count":35},{"year":2024,"count":36},{"year":2025,"count":26},{"year":2026,"count":27}],"oa_status":"bronze","license":"CC BY NC ND","oa_locations":[{"url":"http://www.cell.com/article/S107476132100412X/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S107476132100412X/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S107476132100412X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S107476132100412X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.immuni.2021.10.006","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34758338","host_type":"repository"},{"url":"http://hdl.handle.net/20.500.11850/515038","host_type":"repository"},{"url":"https://hdl.handle.net/10281/504781","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8585508","host_type":"repository"},{"url":"https://doi.org/10.3929/ethz-b-000515038","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8585508","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.3929/ethz-b-000515038","host_type":""},{"url":"http://dx.doi.org/10.1016/j.immuni.2021.10.006","host_type":""},{"url":"https://dx.doi.org/10.1016/j.immuni.2021.10.006","host_type":""},{"url":"https://hdl.handle.net/20.500.14243/522230","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585508/","host_type":""},{"url":"https://hdl.handle.net/20.500.14243/418637","host_type":""}],"fields_of_study":["Neuroinflammation and Neurodegeneration Mechanisms","Reproductive System and Pregnancy","Tryptophan and brain disorders","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Animals","Disease Models, Animal","Disease Susceptibility","Female","Hippocampus","Synaptic Transmission","Neurons","Pregnancy","Prenatal Exposure Delayed Effects","Synapses","Signal Transduction","Interleukin-6","Cytokines","Maternal Exposure","Inflammation Mediators","Mice"],"keywords":["Glutamatergic","Synaptogenesis","Offspring","Biology","Neuroscience","Synapse","Hippocampal formation","Pregnancy","Glutamate receptor","Genetics","Receptor","IL-6","Stat3","neuroinflammation","Brain Connectivity","Glutamatergic Transmission","Neurodevelopmental Disorder","RGS4","Synaptic Development","Maternal Immune Activation","Pro-inflammatory Cytokines","single-cell sequencing","Hippocampus","Synaptic Transmission","Article","Mice","Animals","Neurons","Interleukin-6","brain connectivity; 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