Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), which may be related to mitophagy failure. Previous reports suggest that treadmill exercise protects against mitochondrial dysfunction in AD. However, few studies have investigated the relationship between mitophagy and mitochondrial adaptation caused by treadmill exercise in AD. The current study aimed to investigate whether exercise-ameliorated AD is associated with changes in mitophagy activity. Both Wild-type and APP/PS1 transgenic mice were divided into sedentary (WTC and ADC) and exercise (WTE and ADE) groups (n = 9 for each group). WTE and ADE mice were subjected to treadmill exercise for 12 weeks, followed by evaluating the effect of treadmill exercise on learning and memory ability, Aβ plaques, mitochondrial Aβ peptide level, synaptic activity and mitochondrial function. Meanwhile, mitophagy-related proteins PINK1, Parkin, LC3II and P62 were measured in the hippocampal mitochondrial fractions. The results indicated that exercise not only restored learning and memory ability, but also reduced Aβ plaque area, mitochondrial Aβ peptide level, and increased levels of synaptic markers SYN and GAP43, as well as reversed mitochondrial dysfunction (defective mitochondrial ultrastructure, decreased PGC-1α, TFAM and ATP levels) in APP/PS1 transgenic mice. Moreover, exercise increased mitophagy activity as evidenced by a significant decrease in levels of P62 and PINK1 as well as an increase in levels of LC3II and Parkin in ADE mice. These findings suggest that treadmill exercise can enhance mitophagy activity in the hippocampus, which is efficient in ameliorating pathological phenotypes of APP/PS1 transgenic mice.

中文翻译：

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跑步机锻炼可减轻Aβ诱导的线粒体功能障碍，并增强APP / PS1转基因小鼠的线粒体活性。

线粒体功能障碍是阿尔茨海默氏病（AD）的标志，可能与线粒体衰竭有关。先前的报道表明，跑步机锻炼可预防AD的线粒体功能障碍。但是，很少有研究调查AD运动中跑步引起的线粒体与线粒体适应性之间的关系。当前的研究旨在调查运动改善的AD是否与线粒体活动的改变有关。将野生型和APP / PS1转基因小鼠分为久坐（WTC和ADC）和运动（WTE和ADE）组（每组n = 9）。对WTE和ADE小鼠进行跑步运动12周，然后评估跑步运动对学习和记忆能力，Aβ斑块，线粒体Aβ肽水平，突触活动和线粒体功能。同时，在海马线粒体级分中检测了与线粒体相关的蛋白PINK1，Parkin，LC3II和P62。结果表明，运动不仅可以恢复学习和记忆能力，还可以减少Aβ斑块面积，线粒体Aβ肽水平，增加突触标记SYN和GAP43的水平，以及逆转的线粒体功能障碍（线粒体超微结构缺陷，PGC-1α降低） ，TFAM和ATP水平）。此外，运动增加了线粒体的吞噬能力，​​ADE小鼠中P62和PINK1的水平显着降低，以及LC3II和Parkin的水平显着提高。这些发现表明，跑步机锻炼可以增强海马的线粒体活动，