Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China.
Neuroscience. 2012 Mar 15;205:10-7. doi: 10.1016/j.neuroscience.2011.12.053. Epub 2012 Jan 8.
Stroke is a major cause of death worldwide. Previous studies have suggested both exercise and mitochondrial biogenesis contribute to improved post-ischemic recovery of brain function. However, the exact mechanism underlying this effect is unclear. On the other hand, the benefit of exercise-induced mitochondrial biogenesis in brain has been confirmed. In this study, we attempted to determine whether treadmill exercise induces functional improvement through regulation of mitochondrial biogenesis after brain ischemia. We subjected adult male rats to ischemia, followed by either treadmill exercise or non-exercise and analyzed the effect of exercise on the amount of mitochondrial DNA (mtDNA), expression of mitochondrial biogenesis factors, and mitochondrial protein. In the ischemia-exercise group, only peroxisome proliferator activated receptor coactivator-1 (PGC-1) expression was increased significantly after 3 days of treadmill training. However, after 7 days of training, the levels of mtDNA, nuclear respiratory factor 1, NRF-1, mitochondrial transcription factor A, TFAM, and the mitochondrial protein cytochrome C oxidase subunit IV (COXIV) and heat shock protein-60 (HSP60) also increased above levels observed in non-exercised ischemic animals. These changes followed with significant changes in behavioral scores and cerebral infarct volume. The results indicate that exercise can promote mitochondrial biogenesis after ischemic injury, which may serve as a novel component of exercise-induced repair mechanisms of the brain. Understanding the molecular basis for exercise-induced neuroprotection may be beneficial in the development of therapeutic approaches for brain recovery from the ischemic injury. Based upon our findings, stimulation or enhancement of mitochondrial biogenesis may prove a novel neuroprotective strategy in the future.
中风是全球范围内主要的死亡原因之一。之前的研究表明，运动和线粒体生物发生都有助于改善脑缺血后的功能恢复。然而，这种效应的确切机制尚不清楚。另一方面，运动诱导的脑线粒体生物发生的益处已得到证实。在这项研究中，我们试图确定跑步机运动是否通过调节脑缺血后线粒体生物发生来诱导功能改善。我们使成年雄性大鼠发生缺血，然后进行跑步机运动或不运动，并分析运动对线粒体 DNA（mtDNA）数量、线粒体生物发生因子表达和线粒体蛋白的影响。在缺血-运动组中，只有过氧化物酶体增殖物激活受体共激活因子-1（PGC-1）的表达在跑步机训练 3 天后显著增加。然而，在 7 天的训练后，mtDNA、核呼吸因子 1、NRF-1、线粒体转录因子 A、TFAM、线粒体蛋白细胞色素 C 氧化酶亚基 IV（COXIV）和热休克蛋白-60（HSP60）的水平也高于未运动的缺血动物。这些变化伴随着行为评分和脑梗死体积的显著变化。结果表明，运动可以促进缺血损伤后的线粒体生物发生，这可能是运动诱导的脑修复机制的一个新组成部分。了解运动诱导的神经保护的分子基础可能有助于开发从缺血损伤中恢复大脑的治疗方法。基于我们的发现，刺激或增强线粒体生物发生可能在未来成为一种新的神经保护策略。
