title: Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase.
abstract: Improving mitochondrial function has been proposed as a reasonable therapeutic strategy to reduce amyloid-β (Aβ) load and to modify the progression of Alzheimer's disease (AD). However, the relationship between mitochondrial adaptation and brain neuroprotection caused by physical exercise in AD is poorly understood. This study was undertaken to investigate the effects of long-term treadmill exercise on mitochondrial 8-oxoguanine DNA glycosylase-1 (OGG1) level, mtDNA oxidative damage, and mitochondrial function in the hippocampus of APP/PS1 transgenic mouse model of AD. In the present study, twenty weeks of treadmill training significantly improved the cognitive function and reduced the expression of Aβ-42 in APP/PS1 transgenic (Tg) mice. Training also ameliorated mitochondrial respiratory function by increasing the complexes I, and IV and ATP synthase activities, whereas it attenuated ROS generation and mtDNA oxidative damage in Tg mice. Furthermore, the impaired mitochondrial antioxidant enzymes and mitochondrial OGG1 activities seen in Tg mice were restored with training. Acetylation level of mitochondrial OGG1 and MnSOD was markedly suppressed in Tg mice after exercise training, in parallel with increased level of SIRT3. These findings suggest that exercise training could increase mtDNA repair capacity in the mouse hippocampus, which in turn would result in protection against AD-related mitochondrial dysfunction and phenotypic deterioration.
authors.affiliation: Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of Sport, Tianjin 300381, China ; Department of Military Training Medicines, Logistics University of Chinese People's Armed Police Force, Tianjin 300162, China.
authors.forename: Hai
authors.identifier: 0000-0003-2781-9457
authors.initials: H
authors.lastname: Bo
authors.affiliation: Department of Interventional Neuroradiology, Chinese People's Second Artillery General Hospital, Beijing 100080, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Kang
authors.affiliation: Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of Sport, Tianjin 300381, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of Sport, Tianjin 300381, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of Sport, Tianjin 300381, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of Sport, Tianjin 300381, China ; Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Li Li
authors.initials: LL
authors.lastname: Ji
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D000818:Animals; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics; D004195:Disease Models, Animal; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D010446:Peptide Fragments / Q000096:biosynthesis; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011897:Random Allocation
chemical_list: D016229:Amyloid beta-Peptides; D004272:DNA, Mitochondrial; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse