Activation of liver X receptors protects oligodendrocytes in CA3 of stress-induced mice

作者全名："Zhu, Peilin; Tang, Jing; Liang, Xin; Luo, Yanmin; Wang, Jin; Li, Yue; Xiao, Kai; Li, Jing; Deng, Yuhui; Jiang, Lin; Xiao, Qian; Qi, Yingqiang; Xie, Yuhan; Yang, Hao; Zhu, Lin; Tang, Yong; Huang, Chunxia"

作者地址："[Zhu, Peilin; Tang, Jing; Wang, Jin; Li, Yue; Xiao, Kai; Deng, Yuhui; Xie, Yuhan; Yang, Hao; Zhu, Lin; Tang, Yong] Chongqing Med Univ, Dept Histol & Embryol, Chongqing, Peoples R China; [Zhu, Peilin; Tang, Jing; Liang, Xin; Luo, Yanmin; Wang, Jin; Li, Yue; Xiao, Kai; Li, Jing; Deng, Yuhui; Xie, Yuhan; Yang, Hao; Zhu, Lin; Tang, Yong; Huang, Chunxia] Chongqing Med Univ, Lab Stem Cells & Tissue Engn, Chongqing, Peoples R China; [Liang, Xin] Chongqing Med Univ, Dept Pathophysiol, Chongqing, Peoples R China; [Luo, Yanmin; Li, Jing; Huang, Chunxia] Chongqing Med Univ, Dept Physiol, Chongqing, Peoples R China; [Jiang, Lin] Chongqing Med Univ, Lab Teaching & Management Ctr, Chongqing, Peoples R China; [Xiao, Qian] Chongqing Med Univ, Dept Radioact Med, Chongqing, Peoples R China; [Qi, Yingqiang] Chongqing Med Univ, Inst Life Sci, Dept Electron Microscope, Chongqing, Peoples R China"

通信作者："Huang, CX (通讯作者)，Chongqing Med Univ, Lab Stem Cells & Tissue Engn, Chongqing, Peoples R China.; Huang, CX (通讯作者)，Chongqing Med Univ, Dept Physiol, Chongqing, Peoples R China."

来源：FRONTIERS IN PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000838152900001

JCR分区：Q1

影响因子：5.6

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：liver X receptors agonist; depression; chronic unpredictable stress; oligodendrocyte; CA3

摘要："Depression is a complex disorder that is associated with various structural abnormalities. Oligodendrocyte (OL) dysfunction is associated with the pathogenesis of depression and the promotion of hippocampal oligodendrocyte maturation and myelination could be a novel therapeutic strategy for ameliorating depressive behaviors. Recent studies have shown that activation of liver X receptors (LXRs) by GW3965 improves depressive phenotypes, but the effects of GW3965 on OL function and myelination in the hippocampus of depression remain relatively unclear. To address this issue, we investigated the effects of GW3965 on mature OL in the hippocampus and on the myelin sheaths of mice subjected to chronic unpredictable stress (CUS). Behavioral tests were performed to assess depressive behaviors. Then, the number of mature OLs (CC1(+)) in each hippocampal subregion was precisely quantified with immunohistochemical and stereological methods, and the density of newborn mature OLs (BrdU(+)/Olig2(+)/CC1(+) cells) in each hippocampal subregion was quantified with immunofluorescence. In addition, myelin basic protein (MBP) staining intensity in the cornu ammonis 3 (CA3) region was assessed by using immunofluorescence. We found that both the number of CC1(+) OLs and the density of BrdU(+)/Olig2(+)/CC1(+) cells were obviously decreased in each hippocampal subregion of mice subjected to CUS, and 4 weeks of GW3965 treatment reversed these effects only in the CA3 region. Furthermore, the decreased MBP expression in the CA3 region of mice subjected to CUS was ameliorated by GW3965 treatment. Collectively, these results suggested that improvement of OL maturation and enhancement of myelination may be structural mechanisms underlying the antidepressant effects of LXR agonists."

基金机构：Natural Science Foundation of China (NSFC) [81501156]; General Project of Chongqing Frontier and Applied Basic Research Project [2015jcyjA10020]

基金资助正文："This work was supported in part by the Natural Science Foundation of China (NSFC, 81501156); The General Project of Chongqing Frontier and Applied Basic Research Project (No.cstc 2015jcyjA10020)."