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Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats

LUO Jie¹, WANG Jing-Qiong¹, XIE Li-Na¹, MENG An-Na², ZHENG Si-Si², ZHOU Shou-Hong^2,3,*

¹College of Physical Education, Hunan First Normal College, Changsha 410205, China；²Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin 541199, China；³Department of Physiology, Basic Medical College, Guilin Medical University, Guilin 541199, China

Abstract

This paper was aimed to investigate the effect of voluntary wheel running exercise on depression-like behavior induced by chronic water immersion restraint stress (CWIRS) and the underlying mechanism. Sprague-Dawley (SD) rats received CWIRS to induce depression-like behavior and 4-week voluntary wheel running exercise. Meanwhile, the rats were treated with lipopolysaccharide (LPS) or STAT3 over-expression vector (pcDNA-STAT3) by intracerebroventricular injection. Behavioral tests were used to detect depression-like behavior. ELISA assay was used to detect levels of various inflammatory factors in the rat hippocampus. Western blot was used to detect protein expression levels of ionized calcium binding adaptor molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), phosphorylated STAT3 (p-STAT3) and total STAT3 (t-STAT3). The results showed that, compared with stress group, stress + exercise group exhibited improved depression-like behavior, decreased interleukin-1β (IL-1β) and IL-6 levels, increased IL-4 and IL-10 levels, down-regulated Iba-1 and iNOS protein expression levels, up-regulated Arg1 protein expression level, and decreased p-STAT3/t-STAT3 ratio in hippocampal tissue. LPS reversed the improving effect of voluntary wheel running exercise on depression-like behavior in rats, and the over-expression of STAT3 reversed the promoting effects of voluntary wheel running on M2 polarization of microglial cells in rat hippocampus and depression-like behavior. These results suggest that voluntary wheel running ameliorates the depression-like behavior induced by CWIRS in rats, and the mechanism may be related to regulating hippocampal microglia polarization via STAT3 signaling pathway.

Key words: voluntary wheel running exercise; chronic water immersion restraint stress; depression-like behavior; hippocampus; microglia polarization; STAT3

Received: 　　Accepted:

Corresponding author: 周寿红　　E-mail: zhoushouhong@126.com

DOI: 10.13294/j.aps.2022.0029

Citing This Article：

LUO Jie, WANG Jing-Qiong, XIE Li-Na, MENG An-Na, ZHENG Si-Si, ZHOU Shou-Hong. Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats. Acta Physiol Sin 2022; 74 (2): 177-187 (in Chinese with English abstract).