1. Treadmill Exercise Attenuates Aβ-Induced Mitochondrial Dysfunction and Enhances Mitophagy Activity in APP/PS1 Transgenic Mice
- Author
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Xianliang Zhang, Baixia Li, Jie Xia, Na Zhao, Qing-Wei Yan, Ling-Yu Yin, and Bo Xu
- Subjects
0301 basic medicine ,Genetically modified mouse ,Male ,medicine.medical_specialty ,Hippocampus ,PINK1 ,Mice, Transgenic ,Hippocampal formation ,Biochemistry ,Parkin ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,Internal medicine ,Physical Conditioning, Animal ,Mitophagy ,medicine ,Presenilin-1 ,Animals ,Gap-43 protein ,Maze Learning ,Amyloid beta-Peptides ,biology ,business.industry ,General Medicine ,TFAM ,Mitochondria ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,biology.protein ,Exercise Test ,business ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2019