高强度间歇运动训练上调APP/PS1转基因阿尔兹海默病小鼠海马线粒体自噬的研究

High-intensity interval training-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitophagy

目的:观察高强度间歇运动训练干预是否能改善APP/PS1转基因AD小鼠病理表现,并探讨线粒体自噬在其间的生物学效应。方法:8月龄雄性APP/PS1转基因小鼠分为转基因模型安静组(SED-Tg)和转基因模型+高强度间歇运动训练组(HIIT-Tg),C57BL/6野生型小鼠纳入野生型安静组(SED-Wt)。HIIT-Tg组动物进行12周高强度间歇运动训练。避暗被动回避实验检测学习记忆能力,JC-1荧光探针检测海马线粒体膜电位,二氯荧光素探针检测海马线粒体ROS,Western Blot法检测脑海马Aβ-42、BDNF、AMPK、PINK1、Parkin、Bnip3蛋白表达。结果:①SED-Tg组与SED-Wt组比较,逃避潜伏期、线粒体膜电位、BDNF、AMPK、PINK1、Parkin和Bnip3蛋白表达显著降低(P<0.05—0.01),线粒体ROS产生速率和Aβ-42蛋白表达显著升高(P<0.01)。②HIIT-Tg组与SED-Tg组比较,逃避潜伏期、线粒体膜电位、BDNF、AMPK、PINK1和Parkin蛋白表达显著升高(P<0.01),线粒体ROS产生速率和Aβ-42蛋白表达显著降低(P<0.01)。结论:高强度间歇运动训练可通过上调AMPK-PINK1/Parkin介导的线粒体自噬,改善线粒体功能,减少APP/PS1转基因AD小鼠脑海马Aβ积聚,提高记忆和学习能力。

Objective:To observe the effect of high-intensity interval training on hippocampus in APP/PS1 transgenic mice,as well as the role of mitophagy.Method:Male 8-month APP/PS1 transgenic mice were divided into two groups:sedentary APP/PS1 transgenic mice group(SED-Tg),and high-intensity interval training APP/PS1 transgenic mice group(HIIT-Tg).C57BL/6 wile-type mice were placed in sedentary wild type mice group(SED-Wt).HIIT-Tg mice were subjected to a high-intensity interval training for 12 weeks.Learning ability and memory were evaluated by passive avoidance test.Mitochondrial membrane potential was measured by JC-1 probe.Mitochondrial ROS production was monitored using the dichlorofluorescin diacetate.The protein expressions of Aβ-42,BDNF,AMPK,PINK1,Parkin and Bnip3 were detected by western blotting.Result:①Comparing with SED-Wt group,the retention latency time,membrane potential,protein expressions of BDNF,AMPK,PINK1,Parkin and Bnip3 showed dramatic decrease in SED-Tg group(P<0.05—0.01),while ROS production and Aβ-42 level increased significantly(P<0.01).②Comparing with SED-Tg group,the retention latency time,membrane potential,protein expressions of BDNF,AMPK,PINK1 and Parkin showed dramatic increase in HIIT-Tg group(P<0.01),while ROS production and Aβ-42 level decreased significantly(P<0.01).Conclusion:High-intensity interval training could enhance AMPK-PINK1/Parkin-mediated mitophagy,which in turn ameliorate mitochondrial dysfunction,Aβdeposition and cognitive impairment in hippocampus of APP/PS1 transgenic mice.