GLUTAMATE-INDUCED NEURONAL DEATH - A SUCCESSION OF NECROSIS OR APOPTOSIS DEPENDING ON MITOCHONDRIAL-FUNCTION
GLUTAMATE-INDUCED NEURONAL DEATH - A SUCCESSION OF NECROSIS OR APOPTOSIS DEPENDING ON MITOCHONDRIAL-FUNCTION
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DOI：
10.1016/0896-6273(95)90186-8
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发表时间：
1995-10-01
期刊：
影响因子：
16.2
通讯作者：
NICOTERA, P
中科院分区：
文献类型：
--
作者：
ANKARCRONA, M;DYPBUKT, JM;NICOTERA, P
在缺血性脑损伤期间，谷氨酸积累导致突触后谷氨酸受体的过度刺激，伴随细胞内Ca 2+超载和神经元细胞死亡。在这里，我们表明，谷氨酸可以诱导小脑颗粒细胞培养的早期坏死或延迟凋亡。在暴露于谷氨酸盐期间和之后不久，神经元的亚群因坏死而死亡。在这些细胞中，线粒体膜电位崩溃，细胞核肿胀，细胞内碎片分散在孵育介质中。存活的早期坏死阶段的神经元恢复线粒体电位和能量水平。后来，它们经历了凋亡，如凋亡细胞核的形成和染色质降解成高分子量和低分子量片段所示。这些结果表明，线粒体功能是决定兴奋性毒性中神经元死亡模式的关键因素。
During ischemic brain injury, glutamate accumulation leads to overstimulation of postsynaptic glutamate receptors with intracellular Ca2+ overload and neuronal cell death. Here we show that glutamate can induce either early necrosis or delayed apoptosis in cultures of cerebellar granule cells. During and shortly after exposure to glutamate, a subpopulation of neurons died by necrosis. In these cells, mitochondrial membrane potential collapsed, nuclei swelled, and intracellular debris were scattered in the incubation medium. Neurons surviving the early necrotic phase recovered mitochondrial potential and energy levels. Later, they underwent apoptosis, as shown by the formation of apoptotic nuclei and by chromatin degradation into high and low molecular weight fragments. These results suggest that mitochondrial function is a critical factor that determines the mode of neuronal death in excitotoxicity.