Sex Differences of Microglia and Synapses in the Hippocampal Dentate Gyrus of Adult Mouse Offspring Exposed to Maternal Immune Activation

Frontiers in Cellular Neuroscience

Kaushik Sharma¹  Xiao Luo¹  Étienne Gervais¹  Kanchan Bisht¹  Chin Wai Hui¹  Félix Michaud¹  Marie-Ève Tremblay²  Lisa Topolnik³  Haley A. Vecchiarelli⁵  Lisa Scheefhals⁶ 

[1] Axe neurosciences, Centre de Recherche, Centre Hospitalier Universitarie de Qu-Université Laval, Québec, QC, Canada;Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada;Department of Biochemistry, Microbiology, and Bioinformatics, Faculty of Science and Engineering, Université Laval, Québec, QC, Canada;Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada;Division of Medical Sciences, University of Victoria, Victoria, BC, Canada;Master Neuroscience and Cognition, Faculty of Science, Utrecht University, Utrecht, Netherlands;Neurology and Neurosurgery Department, McGill University, Montréal, QC, Canada;

关键词: microglia;    schizophrenia;    maternal immune activation;    complement;    dentate gyrus;    phagocytosis;   

DOI  :  10.3389/fncel.2020.558181

来源: DOAJ

【 摘 要 】

Schizophrenia is a psychiatric disorder affecting ∼1% of humans worldwide. It is earlier and more frequently diagnosed in men than woman, and men display more pronounced negative symptoms together with greater gray matter reductions. Our previous findings utilizing a maternal immune activation (mIA) mouse model of schizophrenia revealed exacerbated anxiety-like behavior and sensorimotor gating deficits in adult male offspring that were associated with increased microglial reactivity and inflammation in the hippocampal dentate gyrus (DG). However, both male and female adult offspring displayed stereotypy and impairment of sociability. We hypothesized that mIA may lead to sex-specific alterations in microglial pruning activity, resulting in abnormal synaptic connectivity in the DG. Using the same mIA model, we show in the current study sex-specific differences in microglia and synapses within the DG of adult offspring. Specifically, microglial levels of cluster of differentiation (CD)68 and CD11b were increased in mIA-exposed females. Sex-specific differences in excitatory and inhibitory synapse densities were also observed following mIA. Additionally, inhibitory synaptic tone was increased in DG granule cells of both males and females, while changes in excitatory synaptic transmission occurred only in females with mIA. These findings suggest that phagocytic and complement pathways may together contribute to a sexual dimorphism in synaptic pruning and neuronal dysfunction in mIA, and may propose sex-specific therapeutic targets to prevent schizophrenia-like behaviors.

【 授权许可】

Unknown