Preservation of mitochondrial integrity and energy metabolism during experimental status epilepticus leads to neuronal apoptotic cell death in the hippocampus of the rat
Preservation of mitochondrial integrity and energy metabolism during experimental status epilepticus leads to neuronal apoptotic cell death in the hippocampus of the rat
复制标题
DOI：
10.1016/j.seizure.2009.03.002
复制
发表时间：
2009-07-01
影响因子：
3
通讯作者：
Chang, Wen-Neng
中科院分区：
文献类型：
--
作者：
Chuang, Yao-Chung;Lin, Jui-Wei;Chang, Wen-Neng
癫痫持续状态导致海马区线粒体损伤或功能障碍，以及优先选择的神经细胞丢失。由于最终细胞死亡命运的关键决定因素在于细胞内的ATP浓度，我们研究了线粒体的完整性和能量代谢水平是否与特定海马神经元群体中的细胞凋亡有关。采用红藻氨酸(KA)诱导的实验性颞叶癫痫持续状态模型。分别于单侧CA3区微量注射小剂量KA(0.5nmol)后1、3、7d，进行双侧海马区DNA片段化、TUNEL免疫组织化学染色、caspase-3免疫荧光双标染色、电子显微镜观察或ATP含量测定。在一侧CA3区微量注射K-A诱导持续癫痫发作7d后，双侧海马区出现特征性的生化(DNA片段化)、组织化学(TUNEL或活化的caspase-3染色)或超微结构(电子显微镜)的凋亡细胞死亡特征。同时，两侧CA3或CA1亚区的ATP水平维持不变：海马神经元内相对完整的线粒体、粗面内质网、高尔基体或细胞膜等呈现细胞凋亡的超微结构特征。死亡。我们的结果表明，在实验性颞叶癫痫持续状态期间，线粒体超微结构的完整性和能量代谢的维持与海马CA3或CA1神经元的凋亡而不是坏死性细胞死亡具有特异性的相关性。(C)2009年英国癫痫协会。爱思唯尔有限公司出版。保留所有权利。
Status epilepticus results in mitochondrial damage or dysfunction and preferential neuronal cell loss in the hippocampus. Since a critical determinant of the eventual cell death fate resides in intracellular ATP concentration, we investigated whether mitochondrial integrity and level of energy metabolism are related with apoptotic cell death in specific hippocampal neuronal populations. A kainic acid (KA)-induced experimental temporal lobe status epilepticus model was used. Qualitative and quantitative analysis of DNA fragmentation, TUNEL immunohistochemistry, double immunofluorescence staining for activated caspase-3, electron microscopy or measurement of ATP level in the bilateral hippocampus was carried out 1, 3 or 7 days after microinjection unilaterally of a low dose of KA (0.5 nmol) into the CA3 hippocampal subfield. Characteristic biochemical (DNA fragmentation), histochemical (TUNEL or activated caspase-3 staining) or ultrastructural (electron microscopy) features of apoptotic cell death were presented bilaterally in the hippocampus 7 days after the elicitation of sustained hippocampal seizure activity by microinjection of K-A into the unilateral CA3 subfield. At the same time, CA3 or CA1 subfield on either side manifested a maintained ATP level: alongside relatively intact mitochondria, rough endoplasmic reticulum, Golgi apparatus or cytoplasmic membrane in hippocampal neurons that exhibited ultrastructural features of apoptotic cell. death. Our results demonstrated that preserved mitochondrial ultrastructural integrity and maintained energy metabolism during experimental temporal lobe status epilepticus is associated specifically with apoptotic, not necrotic, cell death in hippocampal CA3 or CA1 neurons. (C) 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.