Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Neuroscience. 2011 May 5;181:196-205. doi: 10.1016/j.neuroscience.2011.02.059. Epub 2011 Mar 10.
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-loxP 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).
转录调控因子，神经元抑制因子（NRSF），也称为抑制元件-1 沉默转录因子（REST），在神经发生和各种神经元疾病（如缺血、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。先前的研究表明，NRSF 调节体外乙醇对神经元细胞的作用，然而，NRSF 在乙醇诱导的神经元细胞死亡中的作用尚不清楚。我们使用 Cre-loxP 系统生成 nrsf 条件性敲除小鼠，以破坏神经元中 nrsf 及其截断形式的表达。在出生后第 6 天，乙醇显著增加了野生型小鼠大脑中 NRSF 的神经元特异性截断形式 REST4 的表达，而在 nrsf 条件性敲除小鼠中，这种作用减弱。乙醇的凋亡作用在 nrsf 条件性突变小鼠的多个脑区都很明显。这些结果表明，NRSF，特别是 REST4，可能保护发育中的大脑免受乙醇的影响，并提供新的证据表明 NRSF 可以成为胎儿酒精综合征（FAS）的治疗靶点。
