Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity
Ahmed S, Polis B, Jamwal S, Sanganahalli B, MacDowell Kaswan Z, Islam R, Kim D, Bowers C, Giuliano L, Biederer T, Hyder F, Kaffman A. Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity. Brain Behavior And Immunity 2024, 122: 95-109. PMID: 39134183, PMCID: PMC11402597, DOI: 10.1016/j.bbi.2024.08.010.Peer-Reviewed Original ResearchEarly-life adversityModel of early-life adversityContextual fear conditioningLimited beddingFear conditioningSynaptic engulfmentLB miceSynaptic pruningSex-specific deficitsHippocampus of maleSex-specific effectsHippocampal deficitsAdolescent miceHippocampal functionEarly adversityChemogenetic activationSynaptic connectionsBehavioral aberrationsPotential compensatory mechanismsSynaptic abnormalitiesHippocampusAblation of microgliaRodent hippocampusDeficitsWeeks of lifeMicroglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids
Wu J, Zhang J, Chen X, Wettschurack K, Que Z, Deming B, Olivero-Acosta M, Cui N, Eaton M, Zhao Y, Li S, Suzuki M, Chen I, Xiao T, Halurkar M, Mandal P, Yuan C, Xu R, Koss W, Du D, Chen F, Wu L, Yang Y. Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids. Molecular Psychiatry 2024, 29: 2424-2437. PMID: 38499656, DOI: 10.1038/s41380-024-02518-4.Peer-Reviewed Original ResearchAutism spectrum disorderSpine densityAssociated with autism spectrum disorderLower spine densitySynaptic transmissionHuman cellsPost-synapseProtein-truncating mutationsNeurodevelopmental disorder affecting 1Phagocytosis of synapsesNeuro-immune responsesImpaired learningIntellectual disabilityNeuro-immune interactionsHuman genetic studiesRestoring synaptic transmissionReduced synaptic transmissionAblation of microgliaSpectrum disorderResident immune cellsHuman cerebral organoid modelCerebral organoidsBrain developmentCerebral organoid modelSCN2A mutations
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