Enhanced oxidative stress is an early event during development of Alzheimer-like pathologies in presenilin conditional knock-out mice
Enhanced oxidative stress is an early event during development of Alzheimer-like pathologies in presenilin conditional knock-out mice
复制标题
DOI：
10.1016/j.neulet.2008.05.050
复制
发表时间：
2008-07-25
影响因子：
2.5
通讯作者：
Zhao, Zheng
中科院分区：
文献类型：
--
作者：
Gu, Feng;Zhu, Manjie;Zhao, Zheng
小鼠前脑早老素-1（PS 1）和早老素-2（PS 2）的条件性双敲除（PS cDKO）导致进行性记忆功能障碍和前脑变性。大脑中的这些变化概括了阿尔茨海默病（AD）的大多数神经退行性表型。脑组织中的氧化应激与AD密切相关。在这份报告中，我们研究了2，4和7个月的PS cDKO和年龄和性别匹配的对照小鼠（WT）大脑皮层的氧化应激状态。脂质过氧化（MDA作为措施）和蛋白质氧化（蛋白质羰基作为措施）被发现在PS cDKO小鼠在检查的年龄点显着增加，特别是在那些在2个月，这表明氧化应激是一个早期事件，在PS功能丧失。通过Oxyblot分析进一步证实了皮质蛋白的氧化修饰。内源性抗氧化防御（CAT，SOD和GSH-px的措施）的调查显示，对氧化应激的代偿性防御，特别是在早期阶段，在PS cDKO小鼠。皮质胶质细胞酸性蛋白（GFAP）的表达水平随年龄增加而增加，尤其是在2月龄PS cDKO小鼠中，提示氧化应激与炎症反应之间的相互作用关系可能与AD潜在的功能丧失发病机制密切相关。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Conditional double knock-out of presenilin-1 (PS1) and presenilin-2 (PS2) (PS cDKO) in forebrain of mice led to progressive memory dysfunction and forebrain degeneration. These changes in the brain recapitulated most of the neurodegenerative phenotypes of Alzheimer's disease (AD). Oxidative stress in brain tissues is intimately related to AD. In this report, we examined oxidative stress status in cerebral cortex in 2-,4- and 7-month PS cDKO and the age- and gender-matched control mice (WT). Lipid peroxidation (MDA as the measure) and protein oxidation (protein carbonyl as the measure) were found to be significantly increased in PS cDKO mice over the age points examined, notably in those at 2-month, suggesting that oxidative stress is an early event in response to PS loss-of-function. The oxidative modification of cortical proteins was further confirmed by Oxyblot assay. The investigations into endogenous antioxidant defense (CAT, SOD and GSH-px as measures) revealed a compensatory defense against oxidative stress, particularly at the early age stage, in PS cDKO mice. The expression level of cortical glial fibrillary acidic protein (GFAP) increased in an age-related manner, in particular in 2-month PS cDKO mice, suggesting that the interaction relationship between oxidative stress and inflammatory response may be closely associated with the underlying loss-of-function pathogenesis of AD. (C) 2008 Elsevier Ireland Ltd. All rights reserved.