Cheng J, Chen L, Han S, Qin L, Chen N, Wan Z
Zhongxiao Wan, PhD, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Suzhou, 215123, P.R. China, (P) 0186-0512-65883159; (F) 0186-0512-65883159, Email:
J Nutr Health Aging. 2016;20(5):503-8. doi: 10.1007/s12603-015-0616-7.
To determine the effects of treadmill exercise training and rutin intervention independently and in combination on key molecules involved in Alzheimer's disease (AD) pathology and cognitive function in diet induced obese (DIO) mice.
C57BL/6J mice were randomized into 5 groups: chow group, high fat diet group (HFD), HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), HFD combined with treadmill running and rutin group (HRE). At the end of the intervention, Morris water maze test was conducted to assess hippocampal dependent, long term spatial learning and memory retention. Hippocampus and cortex were dissected and the protein expression of key molecules including insulin-degrading enzyme (IDE), Beta-secretase (BACE1), signal transducer and activator of transcription 3 (STAT3), cAMP-response element binding protein (CREB), post-synaptic density protein 95 (PSD-95) and synaptophysin were measured via western blotting.
Exercise and rutin enhances HFD induced cognitive deficits in DIO mice. In the hippocampus, although HFD has no effect on IDE, BACE1, phosphorylation (p)-STAT3 and p-CREB, HR and HE group have elevated protein expression of IDE; meanwhile, p-CREB was elevated in the HE and HRE group. In the cortex, HFD led to induction in BACE1 and reduction in p-STAT3 and PSD95. Rutin or exercise reversed BACE1, p-STAT3 and PSD95 to normal levels.
Treadmill running and rutin could improve HFD induced cognitive impairment, and p-STAT3, p-CREB, BACE1, IDE, and PSD95 are potential mediators involved in the protective effects of rutin or exercise against HFD induced cognitive dysfunction.
确定跑步机运动训练和芦丁干预单独及联合作用对饮食诱导肥胖（DIO）小鼠阿尔茨海默病（AD）病理和认知功能相关关键分子的影响。
将C57BL/6J小鼠随机分为5组：正常饮食组、高脂饮食组（HFD）、高脂饮食加芦丁干预组（HR）、高脂饮食结合跑步机跑步组（HE）、高脂饮食结合跑步机跑步和芦丁组（HRE）。干预结束时，进行莫里斯水迷宫试验以评估海马依赖性长期空间学习和记忆保持能力。解剖海马和皮层，通过蛋白质印迹法检测关键分子胰岛素降解酶（IDE）、β-分泌酶（BACE1）、信号转导和转录激活因子3（STAT3）、环磷酸腺苷反应元件结合蛋白（CREB）、突触后致密蛋白95（PSD-95）和突触素的蛋白表达。
运动和芦丁可改善DIO小鼠由高脂饮食诱导的认知缺陷。在海马中，虽然高脂饮食对IDE、BACE1、磷酸化（p）-STAT3和p-CREB无影响，但HR组和HE组的IDE蛋白表达升高；同时，HE组和HRE组的p-CREB升高。在皮层中，高脂饮食导致BACE1诱导增加，p-STAT3和PSD95减少。芦丁或运动可将BACE1、p-STAT3和PSD95恢复至正常水平。
跑步机跑步和芦丁可改善高脂饮食诱导的认知障碍，p-STAT3、p-CREB、BACE1、IDE和PSD95是芦丁或运动对高脂饮食诱导的认知功能障碍保护作用的潜在介导因子。
