Miniature synaptic currents become neurotoxic to chronically silenced neurons
Miniature synaptic currents become neurotoxic to chronically silenced neurons
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DOI：
10.1093/cercor/bhl037
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发表时间：
2007-06-01
期刊：
影响因子：
3.7
通讯作者：
Segal, Menahem
中科院分区：
文献类型：
--
作者：
Fishbein, Ianai;Segal, Menahem
当长期暴露于河豚毒素（TTX）而失去自发的持续网络活动时，培养的皮质神经元会收缩其树突，失去树突棘，并在1-2周内退化。这些缓慢退化的神经元在死亡前的电生理特性是正常的，但它们表达非常大的微型兴奋性突触后电流（mEPSCs）。α -氨基-5-羟基-3-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂6,7-二硝基喹啉-2,3-二酮（DNQX）对这些mEPSCs的慢性阻断对细胞存活没有影响，然而，矛盾的是，它可以保护ttx沉默的神经元免于退化。ttx处理的神经元也表现出Ca 21清除机制的缺陷。因此，升级的mepsc足以触发慢性沉默神经元的凋亡过程。
When deprived of spontaneous ongoing network activity by chronic exposure to tetrodotoxin (TTX), cultured cortical neurons retract their dendrites, lose dendritic spines, and degenerate over a period of 1-2 weeks. Electrophysiological properties of these slowly degenerating neurons prior to their death are normal, but they express very large miniature excitatory postsynaptic currents (mEPSCs). Chronic blockade of these mEPSCs by the alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist 6,7-Dinitroquinoxaline-2,3-dione (DNQX) had no effect of its own on cell survival, yet, paradoxically, it protected the TTX-silenced neurons from degenerating. TTX-treated neurons also exhibited deficient Ca 21 clearance mechanisms. Thus, upscaled mEPSCs are sufficient to trigger apoptotic processes in otherwise chronically silenced neurons.