Microglial repopulation in the hippocampal dentate gyrus and its effect on improving mood and cognitive impairments in adult mice after traumatic brain injury during adolescence
Objective:To explore the effect and molecular mechanism of microglial repopulation on mood and cognitive impairment in adult mice following traumatic brain injury(TBI)during adolescence.Methods:The TBI mouse model was established using controlled cortical impact(CCI).Forty-eight 5-week-old C57BL/6J mice were randomly allocated into sham,CCI model,CCI+microglial repopulation,and CCI+microglial depletion groups,and tested in adolescence[4 days post injury(dpi)]and adulthood(21 dpi).Immunofluorescence staining was used to detect the effects of PLX5622 feeding on the microglia in the dentate gyrus region of hippocampus in the model group.Behavioral tests(modified neurological severity scores,open field test,elevated O maze test,Y maze spatial recognition test)were used to assess the involvement of microglial repopulation in mood and cognitive impairment in the model group.RT-qPCR was used to measure levels of inflammatory factors and chemokines in the hippocampus of TBI mice with microglial repopulation.Result:After two weeks of PLX5622 feeding,the clearance rate of microglia in the brain of adolescent mice reached 99%,and microglia in hippocampal dentate gyrus region of the repopulation group showed increased branching and elongation compared with that of the model control group both in adolescence and adulthood.Microglial repopulation could reverse TBI-induced impaired neural function,spatial working memory and anxiety-like behavior in adolescent and adult mice.Microglial repopulation could reduce the expression levels of chemokines(CXCL1,CXCL2)and inflammatory factors(IL-6,IL-1β,TNF-α)in the hippocampus of adolescent and adult mice after TBI.Conclusion:Microglial repopulation can alleviate the neuroinflammation in hippocampal dentate gyrus region by improving the overactivation of microglia after TBI,and then improve the neuro-function impairment,anxiety-like behavior and spatial working memory impairment induced by TBI in adolescent and adult mice.
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