Repetitive traumatic brain injury-induced complement C1-related inflammation impairs long-term hippocampal neurogenesis

作者全名：Wang, Jing; Zhang, Bing; Li, Lanfang; Tang, Xiaomei; Zeng, Jinyu; Song, Yige; Xu, Chao; Zhao, Kai; Liu, Guoqiang; Lu, Youming; Li, Xinyan; Shu, Kai

作者地址：[Wang, Jing; Zhao, Kai; Shu, Kai] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Neurosurg, Wuhan, Hubei, Peoples R China; [Wang, Jing] Shanxi Med Univ, Shanxi Bethune Hosp, Tongji Shanxi Hosp, Shanxi Acad Med Sci,Hosp 3,Dept Neurosurg, Taiyuan, Shanxi, Peoples R China; [Zhang, Bing; Li, Lanfang; Tang, Xiaomei; Zeng, Jinyu; Song, Yige; Lu, Youming; Li, Xinyan] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathophysiol, Wuhan, Hubei, Peoples R China; [Zhang, Bing; Li, Lanfang; Tang, Xiaomei; Zeng, Jinyu; Song, Yige; Lu, Youming; Li, Xinyan] Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan, Hubei, Peoples R China; [Zhang, Bing; Li, Lanfang; Tang, Xiaomei; Zeng, Jinyu; Song, Yige; Lu, Youming; Li, Xinyan] Huazhong Univ Sci & Technol, Inst Brain Res, Wuhan Ctr Brain Sci, Wuhan, Hubei, Peoples R China; [Xu, Chao] Chongqing Med Univ, Dept Grad Student, Chongqing, Peoples R China; [Liu, Guoqiang] Hubei Univ Nationalities, Sch Med Sci, Dept Basic Med, Enshi, Hubei, Peoples R China; [Li, Xinyan] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Anat, Wuhan, Hubei, Peoples R China

通信作者：Shu, K (通讯作者)，Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Neurosurg, Wuhan, Hubei, Peoples R China.; Li, XY (通讯作者)，Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathophysiol, Wuhan, Hubei, Peoples R China.; Li, XY (通讯作者)，Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan, Hubei, Peoples R China.; Li, XY (通讯作者)，Huazhong Univ Sci & Technol, Inst Brain Res, Wuhan Ctr Brain Sci, Wuhan, Hubei, Peoples R China.; Li, XY (通讯作者)，Huazhong Univ Sci & Technol, Sch Basic Med, Dept Anat, Wuhan, Hubei, Peoples R China.

来源：NEURAL REGENERATION RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001250034500015

JCR分区：Q1

影响因子：5.9

年份：2025

卷号：20

期号：3

开始页：821

结束页：835

文献类型：Article

关键词：complement C1; dendrite; dentate gyrus; hippocampus; neural stem cell; neurogenesis; neuroinflammation; neurological function; neuron; traumatic brain injury

摘要：Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/beta-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

基金机构：Fundamental Research Program of Shanxi Province of China [20210302124277]; Science Foundation of Shanxi Bethune Hospital [2021YJ13]

基金资助正文：This work was supported by the Fundamental Research Program of Shanxi Province of China, No. 20210302124277 and the Science Foundation of Shanxi Bethune Hospital, No. 2021YJ13 (both to JW).