Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress

作者全名："Liu, Li; Tang, Jing; Liang, Xin; Li, Yue; Zhu, Peilin; Zhou, Mei; Qin, Lu; Deng, Yuhui; Li, Jing; Wang, Yiying; Jiang, Lin; Huang, Dujuan; Zhou, Yuning; Wang, Shun; Xiao, Qian; Luo, Yanmin; Tang, Yong"

作者地址："[Liu, Li; Tang, Jing; Li, Yue; Zhu, Peilin; Zhou, Mei; Qin, Lu; Deng, Yuhui; Li, Jing; Wang, Yiying; Huang, Dujuan; Zhou, Yuning; Wang, Shun; Tang, Yong] Chongqing Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Chongqing 400016, Peoples R China; [Liu, Li; Tang, Jing; Li, Yue; Zhu, Peilin; Qin, Lu; Deng, Yuhui; Li, Jing; Wang, Yiying; Huang, Dujuan; Zhou, Yuning; Wang, Shun; Luo, Yanmin; Tang, Yong] Chongqing Med Univ, Sch Basic Med Sci, Lab Stem Cells & Tissue Engn, Chongqing 400016, Peoples R China; [Liang, Xin] Chongqing Med Univ, Sch Basic Med Sci, Dept Pathol, Chongqing 400016, Peoples R China; [Zhou, Mei; Luo, Yanmin] Chongqing Med Univ, Sch Basic Med Sci, Dept Physiol, Chongqing 400016, Peoples R China; [Jiang, Lin] Chongqing Med Univ, Lab Teaching & Management Ctr, Chongqing 400016, Peoples R China; [Xiao, Qian] Chongqing Med Univ, Sch Basic Med Sci, Dept Radioact Med, Chongqing 400016, Peoples R China"

通信作者："Tang, Y (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Chongqing 400016, Peoples R China.; Luo, YM; Tang, Y (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Lab Stem Cells & Tissue Engn, Chongqing 400016, Peoples R China.; Luo, YM (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Dept Physiol, Chongqing 400016, Peoples R China."

来源：MOLECULAR PSYCHIATRY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001162893300004

JCR分区：Q1

影响因子：9.6

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："Running exercise has been shown to alleviate depressive symptoms. However, the mechanism underlying the antidepressant effects of running exercise is not fully understood. The imbalance of M1/M2 microglia phenotype/polarization and concomitant dysregulation of neuroinflammation play crucial roles in the pathogenesis of depression. Running exercise increases circulating levels of adiponectin which is known to cross the blood-brain barrier and suppress inflammatory responses. AdipoR1 is an adiponectin receptor that is involved in regulating microglial phenotypes and activation states. However, whether running exercise regulates hippocampal microglial phenotypes and neuroinflammation through adiponectin/AdipoR1 to exert its antidepressant effects remains unclear. In the current study, 4 weeks of running exercise significantly alleviated the depressive-like behaviors of chronic unpredictable stress (CUS)-exposed mice. Moreover, running exercise decreased the microglial numbers and altered microglial morphology in three subregions of the hippocampus to restore the M1/M2 balance; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in CUS-exposed mice. These effects may involve elevation of peripheral tissue (adipose tissue and muscle) and plasma adiponectin levels, and hippocampal AdipoR1 levels as well as activation of the AMPK-NF-kappa B/STAT3 signaling pathway by running exercise. When an adeno-associated virus was used to knock down hippocampal AdipoR1, mice showed depressive-like behaviors and alterations in microglia and inflammatory factor expression in the hippocampus that were similar to those observed in CUS-exposed mice. Together, these results suggest that running exercise maintains the M1/M2 balance and inhibits neuroinflammation in the hippocampus of CUS-exposed mice. These effects might occur via adiponectin/AdipoR1-mediated activation of the AMPK-NF-kappa B/STAT3 signaling pathway."

基金机构：National Natural Science Foundation of China (National Science Foundation of China)

基金资助正文："The authors thank all the staff in the Laboratory Animal Center, Chongqing Medical University, People's Republic of China, for providing assistance with the study."