Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways
Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways
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DOI：
10.1016/j.neuroscience.2005.03.064
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Jevtovic-Todorovic, V
中科院分区：
文献类型：
--
作者：
Yon, JH;Daniel-Johnson, J;Jevtovic-Todorovic, V
最近的研究表明，在突触形成高峰期，发育中的大鼠大脑暴露于常用的全身麻醉剂，可以在发育中的大鼠大脑的许多区域引发广泛的凋亡性神经变性，并在以后的生活中引起持续的学习/记忆缺陷。为了了解全身麻醉药诱导神经元凋亡的机制，我们研究了两种常见的凋亡途径-内在和外在途径-在突触发生的不同时间点。我们发现，内源性通路在麻醉暴露早期（两小时内）被激活，如7日龄大鼠（突触形成高峰期）中bcl-X-L的下调、细胞色素c的上调和caspase-9的激活所示，但在14日龄大鼠（突触形成结束）中保持失活。外源性通路在随后（麻醉暴露后6小时内）被激活，如通过7日龄大鼠中Fas蛋白的上调和caspase-8的激活所测量的，但在14日龄大鼠中保持失活。麻醉诱导的凋亡性神经变性是年龄依赖性的，其脆弱性与突触发生的时间密切相关，即发育中的大脑在突触发生的高峰（7天龄）时最敏感，而在突触发生的结束（14天龄）时最不敏感。(c)2005年IBRO。由爱思唯尔有限公司出版。保留所有权利。
It was shown recently that exposure of the developing rat brain during the peak of synaptogenesis to commonly used general anesthetics can trigger widespread apoptotic neurodegeneration in many regions of the developing rat brain and persistent learning/memory deficits later on in life. To understand the mechanism by which general anesthetics induce apoptotic neuronal death we studied two common apoptotic pathways-the intrinsic and the extrinsic pathway-at different time points during synaptogenesis. We found that the intrinsic pathway is activated early on during anesthesia exposure (within two hours), as measured by the down-regulation of bcl-X-L, up-regulation of cytochrome c and the activation of caspase-9 in 7-day-old rats (the peak of synaptogenesis), but remains inactivated in 14-day-old rats (the end of synaptogenesis). The extrinsic pathway is activated later on (within six hours of anesthesia exposure), as measured by the up-regulation of Fas protein and the activation of caspase-8 in 7-day-old rats, but remains inactivated in 14-day-old rats. Anesthesia-induced apoptotic neurodegeneration is age dependent with vulnerability closely correlating with the timing of synaptogenesis, i.e. the developing brain is most sensitive at the peak of synaptogenesis (7 days old) and least sensitive at the end of synaptogenesis (14 days old). (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.