Ketogenic diet reduces Smac/Diablo and cytochrome c release and attenuates neuronal death in a mouse model of limbic epilepsy
Ketogenic diet reduces Smac/Diablo and cytochrome c release and attenuates neuronal death in a mouse model of limbic epilepsy
复制标题
生酮饮食减少边缘癫痫小鼠模型中 Smac/Diablo 和细胞色素 c 的释放并减轻神经元死亡
DOI：
10.1016/j.brainresbull.2012.07.002
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发表时间：
2012-11-01
影响因子：
3.8
通讯作者：
Li, Tianfu
中科院分区：
文献类型：
--
作者：
Luan, Guoming;Zhao, Yanxin;Li, Tianfu
生酮饮食（KD）在治疗难治性癫痫中是有效的，但其抗癫痫作用的分子机制尚未确定。越来越多的证据表明，癫痫发作通过线粒体途径诱导的神经元细胞死亡和癫痫发作可导致线粒体释放细胞色素c，并且我们先前已经表明，Smac/DIABLO易位到细胞质中在边缘系统癫痫发作模型中的脑损伤中起作用。本研究采用海人酸（KA）诱导C57 BL/6小鼠癫痫发作，观察MD对癫痫发作的神经保护作用。杏仁核内微量注射KA诱发的癫痫持续状态导致海马选择性同侧CA 3区神经元死亡，线粒体释放Smac/DIABLO和细胞色素c。我们发现，KD显着减少KA诱导癫痫发作后24小时在同侧CA 3神经元死亡。此外，MD减少了Smac/DIABLO和细胞色素c从线粒体的释放，减弱了癫痫发作后casepase-9和caspase-3的激活。这些结果表明，KD对边缘癫痫发作诱导的脑损伤的神经保护作用，至少部分地与抑制线粒体释放Smac/DIABLO和细胞色素c有关。(C)2012 Elsevier Inc. All rights reserved.
The ketogenic diet (KD) is effective in the treatment of refractory epilepsy, yet the molecular mechanisms underlying its antiepileptic effects have not been determined. There is increasing evidence that neuronal cell death induced by seizures via mitochondrial pathway and seizures can lead to mitochondrial release of cytochrome c, and we have shown previously that translocation of Smac/DIABLO into the cytosol play a role in the brain damage in a model of limbic seizure. In the present study, we explored the neuroprotective effect of MD in C57BL/6 mice with seizures induced by kainic acid (KA). Status epilepticus triggered by intra-amygdaloid microinjection of KA lead to neuronal death in the selective ipsilateral CA3 subfield of the hippocampus and mitochondrial release of Smac/DIABLO and cytochrome c. We found that KD significantly decreased neuronal death in the ipsilateral CA3 at 24 h after KA-induced seizures. Furthermore, MD reduced Smac/DIABLO and cytochrome c release from mitochondria, attenuated activation of casepase-9 and caspase-3 following seizures. These results demonstrate that the neuroprotective effect of KD against brain injury induced by limbic seizures, at least partially, is associated with inhibition of mitochondrial release of Smac/DIABLO and cytochrome c. (C) 2012 Elsevier Inc. All rights reserved.