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: Hai Bo, Weimin Kang, Ning Jiang, Xun Wang, Yong Zhang, Li Li Ji
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2014 Pg. 834502 ( 2014) ISSN: 1942-0994 [Electronic] United States
• PMID: 25538817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• DNA, Mitochondrial
• Peptide Fragments
• amyloid beta-protein (1-42)
• DNA Glycosylases
• Ogg1 protein, mouse

Topics

• Alzheimer Disease (genetics, metabolism, prevention & control)
• Amyloid beta-Peptides (biosynthesis)
• Animals
• DNA Glycosylases (metabolism)
• DNA Repair
• DNA, Mitochondrial (genetics)
• Disease Models, Animal
• Hippocampus (enzymology, metabolism, physiology)
• Male
• Mice
• Mice, Transgenic
• Mitochondria (metabolism, physiology)
• Oxidative Stress (physiology)
• Peptide Fragments (biosynthesis)
• Physical Conditioning, Animal (physiology)
• Random Allocation