ETHANOL-INDUCED NEURODEGENERATION IN NRSF/REST NEURONAL CONDITIONAL KNOCKOUT MICE
ETHANOL-INDUCED NEURODEGENERATION IN NRSF/REST NEURONAL CONDITIONAL KNOCKOUT MICE
复制标题
NRSF/休息神经元条件性敲除小鼠中乙醇诱导的神经变性
DOI：
10.1016/j.neuroscience.2011.02.059
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发表时间：
2011-05-05
期刊：
影响因子：
3.3
通讯作者：
Fei, J.
中科院分区：
文献类型：
--
作者：
Cai, L.;Bian, M.;Fei, J.
转录调节因子神经元限制性沉默因子(NRSF)又称抑制因子-1沉默转录因子(REST)，在神经发生和多种神经元疾病如脑缺血、癫痫和亨廷顿病中发挥重要作用。在这些疾病过程中，神经元的丢失与NRSF的异常表达和/或定位有关。已有研究表明，NRSF在体外可调节乙醇对神经细胞的作用，但NRSF在乙醇诱导的神经细胞死亡中的作用尚不清楚。我们使用Cre-IoxP系统产生了nrsf条件基因敲除小鼠，以破坏nrsf及其截断形式的神经元表达。在出生后第6天，乙醇显著增加了野生型小鼠大脑中神经元特异性截短形式的NRSF-REST4的表达，而这种影响在条件基因敲除小鼠中减弱。在nrsf条件性突变小鼠的多个脑区，乙醇具有明显的细胞凋亡效应。这些结果表明，NRSF，特别是REST4，可以保护发育中的大脑免受酒精的影响，并为NRSF可以成为胎儿酒精综合征(Fas)的治疗靶点提供了新的证据。(C)2011年IBRO。爱思唯尔有限公司出版。保留所有权利。
The transcription regulator, neuron-restrictive silencer factor (NRSF), also known as repressor element-1 silencing transcription factor (REST), plays an important role in neurogenesis and various neuronal diseases such as ischaemia, epilepsy, and Huntington's disease. In these disease processes, neuronal loss is associated with abnormal expression and/or localization of NRSF. Previous studies have demonstrated that NRSF regulates the effect of ethanol on neuronal cells in vitro, however, the role of NRSF in ethanol-induced neuronal cell death remains unclear. We generated nrsf conditional knockout mice using the Cre-IoxP system to disrupt neuronal expression of nrsf and its truncated forms. At postnatal day 6, ethanol significantly increased the expression of REST4, a neuron-specific truncated form of NRSF, in the brains of wild type mice, and this effect was diminished in nrsf conditional knockout mice. The apoptotic effect of ethanol was pronounced in multiple brain regions of nrsf conditional mutant mice. These results indicate that NRSF, specifically REST4, may protect the developing brain from ethanol, and provide new evidence that NRSF can be a therapeutic target in foetal alcohol syndrome (FAS). (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.