Department of Neurology, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan 250012, China.
Neuroscience. 2013 Aug 15;245:157-65. doi: 10.1016/j.neuroscience.2013.04.019. Epub 2013 Apr 15.
Mitochondrial fission has been reported to be involved in oxidative stress, apoptosis and many neurological diseases. However, the role of mitochondrial fission in seizures, which could induce oxidative stress and neuronal loss, remains unknown. In this study, we used pilocarpine to elicit seizures in rats. Meanwhile, we used mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of mitochondrial fission protein dynamin-related protein1 (Drp1), to suppress mitochondrial fission in epileptic model of rats in vivo. We found that mitochondrial fission was increased after seizures and the inhibition of mitochondrial fission by mdivi-1 significantly attenuated oxidative stress and reduced neuronal loss after seizures, shown by the decreased 8-hydroxy deoxyguanosine (8-oHdG) content, the increased superoxide dismutase (SOD) activity, the reduced expression of cytochrome c and caspase3 and the increased surviving neurons in the hippocampus. These results indicated that mitochondrial fission is up-regulated after seizures and the inhibition of mitochondrial fission is protective against neuronal injury in seizures, the underlying mechanism may be through the mitochondria/reactive oxygen species (ROS)/cytochrome c pathway.
线粒体裂变已被报道与氧化应激、细胞凋亡和许多神经疾病有关。然而，线粒体裂变在癫痫发作中的作用仍不清楚，癫痫发作可诱导氧化应激和神经元丢失。在这项研究中，我们使用匹罗卡品在大鼠中诱发癫痫发作。同时，我们使用线粒体分裂抑制剂 1（mdivi-1），一种线粒体分裂蛋白动力相关蛋白 1（Drp1）的选择性抑制剂，在体内癫痫大鼠模型中抑制线粒体裂变。我们发现，癫痫发作后线粒体裂变增加，mdivi-1 抑制线粒体裂变显著减轻了癫痫发作后的氧化应激和神经元丢失，表现为 8-羟基脱氧鸟苷（8-oHdG）含量降低、超氧化物歧化酶（SOD）活性增加、细胞色素 c 和 caspase3 表达减少以及海马中存活神经元增加。这些结果表明，癫痫发作后线粒体裂变上调，抑制线粒体裂变对癫痫发作中的神经元损伤具有保护作用，其潜在机制可能是通过线粒体/活性氧（ROS）/细胞色素 c 途径。
