Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase.
Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase.
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DOI：
10.1155/2014/834502
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发表时间：
2014
影响因子：
--
通讯作者：
Ji LL
中科院分区：
文献类型：
--
作者：
Bo H;Kang W;Jiang N;Wang X;Zhang Y;Ji LL
改善线粒体功能已被认为是降低β淀粉样蛋白（Aβ）负荷和延缓阿尔茨海默病（AD）进展的合理治疗策略。然而，线粒体适应性和运动引起的AD脑神经保护之间的关系知之甚少。本研究旨在探讨长期跑台运动对APP/PS1转基因AD小鼠海马线粒体8-氧代鸟嘌呤DNA糖基化酶-1（OGG 1）水平、线粒体DNA氧化损伤和线粒体功能的影响。在本研究中，20周的跑台训练显著改善了APP/PS1转基因（Tg）小鼠的认知功能，并降低了Aβ-42的表达。训练还通过增加复合物I和IV以及ATP合酶活性来改善线粒体呼吸功能，而它减弱了Tg小鼠中ROS的产生和mtDNA的氧化损伤。此外，受损的线粒体抗氧化酶和线粒体OGG 1的活动在Tg小鼠恢复训练。运动训练后Tg小鼠线粒体OGG 1和MnSOD的乙酰化水平显著降低，同时SIRT 3水平升高。这些研究结果表明，运动训练可以增加小鼠海马mtDNA的修复能力，这反过来又会导致对AD相关的线粒体功能障碍和表型恶化的保护。
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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