Antagonizing LINGO-1 reduces activated microglia and alleviates dendritic spine loss in the hippocampus of APP/PS1 transgenic mice

作者全名："Xie, Yu-han; Jiang, Lin; Zhang, Yi; Deng, Yu-hui; Yang, Hao; He, Qi; Zhou, Yu-ning; Zhou, Chun-ni; Luo, Yan-min; Liang, Xin; Wang, Jin; Huang, Du-juan; Zhu, Lin; Tang, Yong; Chao, Feng-lei"

作者地址："[Xie, Yu-han; Deng, Yu-hui; Yang, Hao; He, Qi; Zhou, Yu-ning; Zhou, Chun-ni; Wang, Jin; Huang, Du-juan; Zhu, Lin; Tang, Yong; Chao, Feng-lei] Chongqing Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Chongqing 400016, Peoples R China; [Xie, Yu-han; Deng, Yu-hui; Yang, Hao; He, Qi; Zhou, Yu-ning; Zhou, Chun-ni; Wang, Jin; Huang, Du-juan; Zhu, Lin; Tang, Yong; Chao, Feng-lei] Chongqing Med Univ, Sch Basic Med Sci, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China; [Jiang, Lin] Chongqing Med Univ, Lab Teaching & Management Ctr, Chongqing 400016, Peoples R China; [Zhang, Yi] Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing 400010, Peoples R China; [Luo, Yan-min] Chongqing Med Univ, Sch Basic Med Sci, Dept Physiol, Chongqing 400016, Peoples R China; [Liang, Xin] Chongqing Med Univ, Sch Basic Med Sci, Dept Pathol, Chongqing 400016, Peoples R China"

通信作者："Tang, Y; Chao, FL (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Chongqing 400016, Peoples R China."

来源：NEUROSCIENCE LETTERS

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001149224600001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：820

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Synapse; Microglia; Hippocampus; Alzheimer 's disease

摘要："In Alzheimer's disease (AD), microglia are involved in synaptic pruning and mediate synapse loss. LINGO-1 is a negative regulator of nerve growth, and whether antagonizing LINGO-1 can attenuate synaptic pruning by microglia and rescue dendritic spines in the hippocampus in AD is still unclear. On this basis, the anti-LINGO-1 antibody, which binds to LINGO-1 protein and antagonizes the effects of LINGO-1, was administered to 10 -month-old APP/PS1 transgenic mice for 2 months. The Morris water maze test, immunohistochemical and stereological methods, immunofluorescence and 3D reconstruction were used. Compared to wild-type mice, APP/ PS1 transgenic mice had worse performance on behavioral tests, fewer dendritic spines but more microglia in the hippocampus. Meanwhile, the microglia in APP/PS1 transgenic mice had more branches of medium length (4-6 mu m) and a cell body area with greater variability. Moreover, APP/PS1 transgenic mice had more postsynaptic termini colocalized with microglia in the hippocampus than wild-type mice. The anti-LINGO-1 antibody significantly reversed these changes in AD, indicating that the anti-LINGO-1 antibody can improve hippocampus-dependent learning and memory abilities and effectively rescue dendritic spines in the hippocampus of AD mice and that microglia might participate in this progression in AD. These results provide a scientific basis for further studying the mechanism of the anti-LINGO-1 antibody in AD and help to elucidate the role of LINGO-1 in the treatment of AD."

基金机构："National Natural Science Foundation of China (NSFC) [82171522, 82002227]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (NSFC, 82171522; NSFC, 82002227) ."