Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Neurosci Lett. 2013 Jun 17;545:64-8. doi: 10.1016/j.neulet.2013.04.026. Epub 2013 Apr 28.
Mdivi-1 is a selective inhibitor of a mitochondrial fission protein Drp1. Recent studies demonstrated that inhibition of Drp1 provides neuroprotection in vitro and in vivo. In this study, we examined the role of mdivi-1 in hippocampal neuron death after seizures induced by pilocarpine. Our data showed that pretreatment with mdivi-1 (1.25 mg/kg) significantly attenuated the neuronal death in hippocampus induced by seizures. This neuroprotective effect was dose-dependent. In addition, the seizures resulted in up-regulation of Drp1 expression and mdivi-1 treatment had no effect on the expression. Moreover, we also found that mdivi-1 (1.25 mg/kg) treatment reversed the release of cytochrome c (CytC), translocation of apoptosis-inducing factor (AIF) induced by seizures while inhibiting the activated caspase-3. Altogether, our data suggested that mdivi-1 exerts neuroprotective effects against cell death of hippocampal neurons induced by seizures, and the underlying mechanism may be through inhibiting CytC release, AIF translocation and suppression of the mitochondrial apoptosis pathway.
Mdivi-1 是一种线粒体分裂蛋白 Drp1 的选择性抑制剂。最近的研究表明，Drp1 的抑制作用可在体外和体内提供神经保护作用。在这项研究中，我们研究了 Mdivi-1 在匹罗卡品诱导的癫痫发作后海马神经元死亡中的作用。我们的数据表明，Mdivi-1（1.25mg/kg）预处理可显著减轻癫痫发作引起的海马神经元死亡。这种神经保护作用呈剂量依赖性。此外，癫痫发作导致 Drp1 表达上调，而 Mdivi-1 处理对其表达没有影响。此外，我们还发现 Mdivi-1（1.25mg/kg）处理可逆转癫痫发作引起的细胞色素 c（CytC）释放、凋亡诱导因子（AIF）的易位，同时抑制激活的 caspase-3。总之，我们的数据表明 Mdivi-1 对癫痫发作引起的海马神经元死亡具有神经保护作用，其潜在机制可能是通过抑制 CytC 释放、AIF 易位和抑制线粒体凋亡途径。
