Exercise Improves High Fat-Induced Cognitive Impairment by Inhibiting Hippocampal Neuroinflammation via the Suppression of TLR4/MyD88/NF-κB Signaling Pathway
Sports Science Institution, Nanjing University, Nanjing, Jiangsu 210046, 1Department of Sports, Henan University of Technology, Zhengzhou, Henan 450001, P. R. China
Y. Zhai, Sports Science Institution, Nanjing University, Nanjing, Jiangsu 210046, P. R. China, E-mail: email@example.com
In the present study, the high fat diet was used to establish a murine model of obesity and treadmill exercise was applied to improve obesity. After exercise intervention, the novel object recognition test and threechambered social test were performed to evaluate cognitive function. Enzyme-linked immunosorbent assay was employed to measure serum inflammatory factor levels and Western blot assay was performed to detect hippocampal protein levels in pro-inflammatory signaling pathway. We found that high fat diet mice spent less time on exploring novel objects and communication with unfamiliar mice in the novel object recognition and three-chambered social test, respectively. The cognitive decline in obese mice was significantly alleviated after treadmill exercise. Furthermore, serum levels of inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 as well as hippocampal tolllike receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B signaling pathway which can lead to the production of pro-inflammatory mediators were remarkably activated in obese mice. According to the random control experimental scheme and its big data analysis we found treadmill exercise inhibited the inflammatory response in the hippocampus. These results suggest that exercise may improve the high fat diet induced cognitive impairment by inhibiting hippocampal inflammation via the suppression of toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B signaling pathway. Our work elucidates the mechanism underlying the improvement of exercise in obesity induced cognitive dysfunction and provides theoretical basis for the clinical application of exercise strategies for the treatment of obese patients with cognitive dysfunction.