期刊
BRAIN RESEARCH BULLETIN
卷 165, 期 -, 页码 30-39出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2020.09.015
关键词
Treadmill exercise; Neuroinflammation; SIRT1; T2DM; BDNF; Cognitive function
资金
- Ministry of education of Humanities and Social Science project [19YJCZH255]
- Shandong Province of humanities and Social Sciences Foundation [18CTYJ11, 20DTYJ06]
Although previous studies showed that exercise can improve cognitive dysfunction in type 2 diabetes (T2DM), the underlying mechanism remains unclear. Sirtuin 1 (SIRT1) has been shown to play a role in regulating in-flammatory responses in the brain and increasing BDNF expression. This study investigated the effects of treadmill exercise on the hippocampal inflammatory response and BDNF expression in a T2DM mice model. We also tested whether these effects are SIRT1-dependent. In this study, C57BL/6 mice were used to construct T2DM model by a high-fat diet and STZ injection. We found that treadmill exercise for 8 weeks can significantly improve the cognitive dysfunction, alleviate activation of proinflammatory microglia M1 (Iba1 labeling) in the hippocampus of T2DM mice, and reduce the levels of proinflammatory factors IL-1 beta, IL-6, TNF-alpha, increase the expression levels of anti-inflammatory factors IL-10, TGF-beta 1, and promote the release of BDNF. We also found that exercise activate the signaling pathway of SIRT1/ NF-kappa B and SIRT1/ PGC-1 alpha/ FNDC5/ BDNF. After the application of nicotinamide (NAM, SIRT1 inhibitor), the positive effects of exercise were remarkably suppressed. Our results showed that long-term moderate intensity treadmill exercise can alleviate inflammatory response in the hippocampus and increase BDNF expression in T2DM mice by activating SIRT1.
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