Pennypacker K R, Yang X, Gordon M N, Benkovic S, Miller D, O'Callaghan J P
University of South Florida, College of Medicine, Department of Pharmacology and Therapeutics, Tampa, FL 33612, USA.
Neuroscience. 2000;101(4):913-9. doi: 10.1016/s0306-4522(00)00381-x.
A long-term induction of Fos-related antigens has been shown in neurons after brain injury, suggesting that Fos-related antigens are involved in enhancing the transcription of genes related to the process of regeneration and repair. In the present study, we report that levels of Fos-related antigen-2 are elevated in several models of chemically induced brain injury. Trimethyltin, which causes degeneration of neurons primarily in the hippocampus and other limbic regions, results in a five-fold induction of Fos-related antigen-2 immunoreactivity in neurons in the pyramidal and dentate layers of the hippocampus starting at seven days post-treatment and persisting for 60days. Methamphetamine and methylenedioxymethamphetamine, agents which cause degeneration of dopaminergic nerve terminals in the striatum of the mouse, cause an increase in Fos-related antigen-2 immunoreactivity which begins at three days post-treatment and returns to basal levels by days 5 and 15, respectively. Treatment with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine elevated levels of Fos-related antigen-2 in the mouse striatum at three days post-treatment. This abbreviated time-course of Fos-related antigen-2 induction is consistent with less severe insult (terminal damage) relative to trimethyltin (cell death), but induction occurs during the period of regeneration and repair in both models. Dexfenfluramine, a non-neurotoxic amphetamine, does not induce Fos-related antigen-2 expression. Decreasing core temperature of the mouse, which blocks amphetamine-induced neurotoxicity, also blocks Fos-related antigen-2 induction. In summary, Fos-related antigen-2 is induced in models of both cell death and terminal degeneration, suggesting that this transcription factor may serve as a universal signal transduction molecule involved in the regulation of genes related to regeneration and repair in the CNS.
脑损伤后，神经元中已显示出Fos相关抗原的长期诱导，这表明Fos相关抗原参与增强与再生和修复过程相关基因的转录。在本研究中，我们报告在几种化学诱导的脑损伤模型中，Fos相关抗原-2的水平升高。三甲基锡主要导致海马体和其他边缘区域的神经元变性，从治疗后7天开始，可使海马体锥体细胞层和齿状层神经元中的Fos相关抗原-2免疫反应性增加5倍，并持续60天。甲基苯丙胺和亚甲基二氧甲基苯丙胺可导致小鼠纹状体中多巴胺能神经末梢变性，它们会引起Fos相关抗原-2免疫反应性增加，分别在治疗后3天开始，在第5天和第15天恢复到基础水平。用1-甲基-4-苯基-1,2,3,6-四氢吡啶治疗后3天，小鼠纹状体中Fos相关抗原-2水平升高。与三甲基锡（细胞死亡）相比，Fos相关抗原-2诱导的这种缩短的时间进程与较轻的损伤（终末损伤）一致，但在两种模型的再生和修复期间均会发生诱导。右芬氟拉明是一种非神经毒性的苯丙胺，不会诱导Fos相关抗原-2表达。降低小鼠的核心体温可阻断苯丙胺诱导的神经毒性，也可阻断Fos相关抗原-2诱导。总之，在细胞死亡和终末变性模型中均诱导出Fos相关抗原-2，这表明该转录因子可能作为一种通用的信号转导分子，参与中枢神经系统中与再生和修复相关基因的调控。
