{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:28:40Z","timestamp":1770816520904,"version":"3.50.1"},"reference-count":82,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["(2019YFA0801900)"],"award-info":[{"award-number":["(2019YFA0801900)"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971139"],"award-info":[{"award-number":["81971139"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770839"],"award-info":[{"award-number":["81770839"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81821091"],"award-info":[{"award-number":["81821091"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171340"],"award-info":[{"award-number":["82171340"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory\u2013inhibitory (<jats:italic>E<\/jats:italic>\/<jats:italic>I<\/jats:italic>) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic\u2010like behavior in mice and a concurrent decreased <jats:italic>E<\/jats:italic>\/<jats:italic>I<\/jats:italic> ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic\u2010like behavior and restores the <jats:italic>E<\/jats:italic>\/<jats:italic>I<\/jats:italic> balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.<\/jats:p>","DOI":"10.1002\/glia.24091","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T11:33:36Z","timestamp":1631187216000},"page":"106-122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Increasing astrogenesis in the developing hippocampus induces autistic\u2010like behavior in mice via enhancing inhibitory synaptic transmission"],"prefix":"10.1002","volume":"70","author":[{"given":"Juan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Lin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of Ophthalmology of the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of Ophthalmology of the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min\u2010Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of Ophthalmology of the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian\u2010Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of Ophthalmology of the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang\u2010Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Core Facilities Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Dong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of Ophthalmology of the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"},{"name":"Department of Pharmacology Zhejiang University City College School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-4734","authenticated-orcid":false,"given":"Yi","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"},{"name":"National Human Brain Bank for Health and Disease  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(93)90124-V"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.056"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.12.026"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10658"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1153"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2275"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.35.6.866"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80937-X"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.02.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09582"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2012.03.016"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.020"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.10.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3484"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.016"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0056-y"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506071102"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.092"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22713"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25610"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3980-04.2005"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09612"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag3194"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111093108"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20519"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-008-0646-7"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22956"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra0708473"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.016"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11356"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1440"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09114-z"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.07.008"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.08.036"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2009.10.004"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3032-07.2008"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22461"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0014-3"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/14734220500208846"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-016-0015-z"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10214"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31129-2"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1897"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0444-3"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06731-y"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5413.479"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.06.002"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0867-07.2007"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.07.033"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0413-20.2020"},{"key":"e_1_2_9_52_1","volume-title":"The mouse brain in stereotaxic coordinates","author":"Paxinos G.","year":"2012"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09965"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.9.1618"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31629"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.08.017"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2018.0145"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.11.019"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18861-3"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2019.03.007"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1297-04.2004"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201605046"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2851"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2014.03.005"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002627"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0426-0"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.2.184"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.037"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1307491"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.045"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22741"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1146221"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.07.040"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng772"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.21-05-01580.2001"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222381"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.03.008"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.06.004"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004190"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.02.014"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.07.021"},{"issue":"2","key":"e_1_2_9_82_1","first-page":"109","article-title":"Astroglia disturbances during development of the central nervous system in fetuses with Down's syndrome","volume":"49","author":"Zdaniuk G.","year":"2011","journal-title":"Folia Neuropathologica"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2019"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24091","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/glia.24091","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T19:53:16Z","timestamp":1692474796000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.24091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,9]]},"references-count":82,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/glia.24091"],"URL":"https:\/\/doi.org\/10.1002\/glia.24091","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,9]]},"assertion":[{"value":"2021-04-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}