解剖学杂志2024，Vol.47Issue(4)：289-294,6.DOI:10.3969/j.issn.1001-1633.2024.04.002
海马齿状回小胶质细胞再殖改善青少年期小鼠创伤性脑损伤成年后的情绪与认知障碍
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
摘要
Abstract
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.关键词
创伤性脑损伤/小胶质细胞/再殖/青少年期/神经炎症Key words
traumatic brain injury/microglia/repopulation/adolescence/neuroinflammation分类
医药卫生引用本文复制引用
王蕾蕾,陶珂,肖虹蕾,刘琼,李文生..海马齿状回小胶质细胞再殖改善青少年期小鼠创伤性脑损伤成年后的情绪与认知障碍[J].解剖学杂志,2024,47(4):289-294,6.基金项目
科技创新2030-"脑科学与类脑研究"重大项目(#2021ZD0201100 （）
#2021ZD0201104) （）
