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Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase.

Bo H, Kang W, Jiang N, Wang X, Zhang Y, Ji LL - Oxid Med Cell Longev (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

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Effects of 20 weeks of treadmill exercise training on activities of mitochondrial complex I (a), complex II (b), complex III, (c), complex IV (d), and ATP synthase activity (e). Group identities are the same as those in Figure 1. Hippocampus from four mice in one group was pooled and mitochondria were isolated for each sample, n = 8 for all independent experiments. Data are mean ± SD. **P < 0.01 compared to SED-WT group. #P < 0.05; ##P < 0.01, compared to SED-Wt or SED-Tg group. n.s., nonsignificant.
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fig4: Effects of 20 weeks of treadmill exercise training on activities of mitochondrial complex I (a), complex II (b), complex III, (c), complex IV (d), and ATP synthase activity (e). Group identities are the same as those in Figure 1. Hippocampus from four mice in one group was pooled and mitochondria were isolated for each sample, n = 8 for all independent experiments. Data are mean ± SD. **P < 0.01 compared to SED-WT group. #P < 0.05; ##P < 0.01, compared to SED-Wt or SED-Tg group. n.s., nonsignificant.

Mentions: In the SED groups, the activities of complex IV and ATP synthase in the hippocampus were significantly decreased in APP/PS1 Tg mice as compared to Wt mice (P < 0.01; Figure 4), while the activities of complexes I, II, and III were similar between the two groups. Training elevated the activities of complexes I and IV and ATP synthase in Tg mice (P < 0.05 or 0.01; Figure 4). In the Wt mice, training significantly increased the activities of complex I and ATP synthase (P < 0.05; Figure 4).


Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase.

Bo H, Kang W, Jiang N, Wang X, Zhang Y, Ji LL - Oxid Med Cell Longev (2014)

Effects of 20 weeks of treadmill exercise training on activities of mitochondrial complex I (a), complex II (b), complex III, (c), complex IV (d), and ATP synthase activity (e). Group identities are the same as those in Figure 1. Hippocampus from four mice in one group was pooled and mitochondria were isolated for each sample, n = 8 for all independent experiments. Data are mean ± SD. **P < 0.01 compared to SED-WT group. #P < 0.05; ##P < 0.01, compared to SED-Wt or SED-Tg group. n.s., nonsignificant.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4236906&req=5

fig4: Effects of 20 weeks of treadmill exercise training on activities of mitochondrial complex I (a), complex II (b), complex III, (c), complex IV (d), and ATP synthase activity (e). Group identities are the same as those in Figure 1. Hippocampus from four mice in one group was pooled and mitochondria were isolated for each sample, n = 8 for all independent experiments. Data are mean ± SD. **P < 0.01 compared to SED-WT group. #P < 0.05; ##P < 0.01, compared to SED-Wt or SED-Tg group. n.s., nonsignificant.
Mentions: In the SED groups, the activities of complex IV and ATP synthase in the hippocampus were significantly decreased in APP/PS1 Tg mice as compared to Wt mice (P < 0.01; Figure 4), while the activities of complexes I, II, and III were similar between the two groups. Training elevated the activities of complexes I and IV and ATP synthase in Tg mice (P < 0.05 or 0.01; Figure 4). In the Wt mice, training significantly increased the activities of complex I and ATP synthase (P < 0.05; Figure 4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus