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Inhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction and behavioral abnormalities

dc.rights.licenseopenen_US
dc.contributor.authorIKEZU, Seiko
dc.contributor.authorYEH, Hana
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorDELPECH, Jean-Christophe
dc.contributor.authorWOODBURY, Maya
dc.contributor.authorVAN ENOO, Alicia
dc.contributor.authorRUAN, Zhi
dc.contributor.authorSIVAKUMARAN, Sudhir
dc.contributor.authorYOU, Yang
dc.contributor.authorHOLLAND, Carl
dc.contributor.authorGUILLAMON-VIVANCOS, Teresa
dc.contributor.authorYOSHII-KITAHARA, Asuka
dc.contributor.authorBOTROS, Mina
dc.contributor.authorMADORE, Charlotte
dc.contributor.authorCHAO, Pin-Hao
dc.contributor.authorDESANI, Ankita
dc.contributor.authorMANIMARAN, Solaiappan
dc.contributor.authorKALAVAI, Srinidhi Venkatesan
dc.contributor.authorJOHNSON, W. Evan
dc.contributor.authorBUTOVSKY, Oleg
dc.contributor.authorMEDALLA, Maria
dc.contributor.authorLUEBKE, Jennifer
dc.contributor.authorIKEZU, Tsuneya
dc.date.accessioned2021-09-27T08:21:52Z
dc.date.available2021-09-27T08:21:52Z
dc.date.issued2020-02
dc.identifier.issn1359-4184en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112395
dc.description.abstractEnAbstract Maternal immune activation (MIA) disrupts the central innate immune system during a critical neurodevelopmental period. Microglia are primary innate immune cells in the brain although their direct influence on the MIA phenotype is largely unknown. Here we show that MIA alters microglial gene expression with upregulation of cellular protrusion/neuritogenic pathways, concurrently causing repetitive behavior, social deficits, and synaptic dysfunction to layer V intrinsically bursting pyramidal neurons in the prefrontal cortex of mice. MIA increases plastic dendritic spines of the intrinsically bursting neurons and their interaction with hyper-ramified microglia. Treating MIA offspring by colony stimulating factor 1 receptor inhibitors induces depletion and repopulation of microglia, and corrects protein expression of the newly identified MIA-associated neuritogenic molecules in microglia, which coalesces with correction of MIA-associated synaptic, neurophysiological, and behavioral abnormalities. Our study demonstrates that maternal immune insults perturb microglial phenotypes and influence neuronal functions throughout adulthood, and reveals a potent effect of colony stimulating factor 1 receptor inhibitors on the correction of MIA-associated microglial, synaptic, and neurobehavioral dysfunctions.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enInhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction and behavioral abnormalities
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41380-020-0671-2en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed32071385en_US
bordeaux.journalMolecular Psychiatryen_US
bordeaux.page1808–1831en_US
bordeaux.volume26en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.teamPsychoneuroimmunologie et Nutrition: Approches expérimentales et cliniquesen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Psychiatry&rft.date=2020-02&rft.volume=26&rft.spage=1808%E2%80%931831&rft.epage=1808%E2%80%931831&rft.eissn=1359-4184&rft.issn=1359-4184&rft.au=IKEZU,%20Seiko&YEH,%20Hana&DELPECH,%20Jean-Christophe&WOODBURY,%20Maya&VAN%20ENOO,%20Alicia&rft.genre=article


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