"Anti-LINGO-1 antibody ameliorates cognitive impairment, promotes adult hippocampal neurogenesis, and increases the abundance of CB1R-rich CCK-GABAergic interneurons in AD mice"

作者全名："He, Qi; Jiang, Lin; Zhang, Yi; Yang, Hao; Zhou, Chun-Ni; Xie, Yu-Han; Luo, Yan-Min; Zhang, Shan-Shan; Zhu, Lin; Guo, Yi-Jing; Deng, Yu-Hui; Liang, Xin; Xiao, Qian; Zhang, Lei; Tang, Jing; Huang, Du-Juan; Zhou, Yu-Ning; Dou, Xiao-Yun; Chao, Feng-Lei; Tang, Yong"

作者地址："[He, Qi; Yang, Hao; Zhou, Chun-Ni; Xie, Yu-Han; Zhang, Shan-Shan; Zhu, Lin; Guo, Yi-Jing; Deng, Yu-Hui; Zhang, Lei; Tang, Jing; Huang, Du-Juan; Zhou, Yu-Ning; Chao, Feng-Lei; Tang, Yong] Chongqing Med Univ, Fac Basic Med Sci, Dept Histol & Embryol, Chongqing 400016, Peoples R China; [He, Qi; Yang, Hao; Zhou, Chun-Ni; Xie, Yu-Han; Zhang, Shan-Shan; Zhu, Lin; Guo, Yi-Jing; Deng, Yu-Hui; Zhang, Lei; Tang, Jing; Huang, Du-Juan; Zhou, Yu-Ning; Chao, Feng-Lei; Tang, Yong] Chongqing Med Univ, Fac Basic Med Sci, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China; [Jiang, Lin] Chongqing Med Univ, Expt Teaching Management Ctr, Chongqing 400016, Peoples R China; [Zhang, Yi] Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Luo, Yan-Min] Chongqing Med Univ, Fac Basic Med Sci, Dept Physiol, Chongqing 400016, Peoples R China; [Liang, Xin] Chongqing Med Univ, Fac Basic Med Sci, Dept Pathophysiol, Chongqing 400016, Peoples R China; [Xiao, Qian] Chongqing Med Univ, Fac Basic Med Sci, Dept Radioact Med, Chongqing 400016, Peoples R China; [Dou, Xiao-Yun] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China"

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

来源：NEUROBIOLOGY OF DISEASE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000677548100004

JCR分区：Q1

影响因子：6.1

年份：2021

卷号：156

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：LINGO-1; CB1R; GABAergic interneurons; Adult hippocampal neurogenesis; Cognitive abilities; AD mice

摘要："In view of the negative regulatory effect of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) on neurons, an antibody against LINGO-1 (anti-LINGO-1 antibody) was herein administered to 10-month-old APP/PS1 transgenic Alzheimer's disease (AD) mice for 2 months as an experimental intervention. Behavioral, stereology, immunohistochemistry and immunofluorescence analyses revealed that the anti-LINGO-1 antibody significantly improved the cognitive abilities, promoted adult hippocampal neurogenesis (AHN), decreased the amyloid beta (A beta) deposition, enlarged the hippocampal volume, and increased the numbers of total neurons and GABAergic interneurons, including GABAergic and CCK-GABAergic interneurons rich in cannabinoid type 1 receptor (CB1R), in the hippocampus of AD mice. In contrast, this intervention significantly reduced the number of GABAergic interneurons expressing LINGO-1 and CB1R in the hippocampus of AD mice. More importantly, we also found a negative correlation between LINGO-1 and CB1R on GABAergic interneurons in the hippocampus of AD mice, while the anti-LINGO-1 antibody reversed this relationship. These results indicated that LINGO-1 plays an important role in the process of hippocampal neuron loss in AD mice and that antagonizing LINGO-1 can effectively prevent hippocampal neuron loss and promote AHN. The improvement in cognitive abilities may be attributed to the improvement in AHN, and in the numbers of GABAergic interneurons and CCK-GABAergic interneurons rich in CB1Rs in the hippocampus of AD mice induced by the anti-LINGO-1 antibody. Collectively, the double target effect (LINGO-1 and CB1R) initiated by the anti LINGO-1 antibody may provide an important basis for the study of drugs for the prevention and treatment of AD in the future."

基金机构："National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81801269, 81671259, 81871073]; Natural Science Foundation of Chongqing, P. R. ChinaNatural Science Foundation of Chongqing [cstc2020jcyjmsxmX0125]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (NSFC, 81801269; NSFC, 81671259; NSFC, 81871073) and the Natural Science Foundation of Chongqing, P. R. China (cstc2020jcyjmsxmX0125) ."