促炎细胞因子
西妥因1
神经炎症
小胶质细胞
海马结构
内分泌学
海马体
内科学
FNDC5
医学
炎症
神经科学
化学
心理学
下调和上调
细胞
基因
纤维连接蛋白
生物化学
作者
Xianshengjie Lang,Na Zhao,Qiang He,Xun Li,Xuejiao Li,Chuanning Sun,Xianliang Zhang
标识
DOI:10.1016/j.brainresbull.2020.09.015
摘要
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 inflammatory 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-1β, IL-6, TNF-α, increase the expression levels of anti-inflammatory factors IL-10, TGF-β1, and promote the release of BDNF. We also found that exercise activate the signaling pathway of SIRT1/ NF-κB and SIRT1/ PGC-1α/ 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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