Effects of high cholesterol diet on gliosis in apolipoprotein E knockout mice implications for Alzheimer's disease and stroke
Effects of high cholesterol diet on gliosis in apolipoprotein E knockout mice implications for Alzheimer's disease and stroke
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DOI：
10.1016/j.neulet.2004.05.057
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发表时间：
2004-10-14
影响因子：
2.5
通讯作者：
Schultzberg, M
中科院分区：
文献类型：
--
作者：
Crisby, M;Rahman, SMA;Schultzberg, M
高胆固醇血症已被认为是阿尔茨海默病（AD）的危险因素。AD的遗传危险因素是载脂蛋白E（apoE）的E4等位基因。ApoE是脑中主要的脂蛋白转运蛋白，主要由神经胶质细胞产生。本研究的重点是分析持续9个月的高胆固醇（HC）饮食对野生型（WT）小鼠和apoE基因无效突变（敲除）小鼠大脑胶质细胞激活的影响。，KO）小鼠。星形胶质细胞和小胶质细胞的活化分别在胶质细胞酸性蛋白（GFAP）和F4/80的免疫组织化学标记后进行分析。此外，抗氧化酶NAD（P）H：醌氧化还原酶（NQO 1）的表达进行了分析。有一个显着的刺激星形胶质细胞和小胶质细胞的活化，以及诱导表达的NQO 1在海马和大脑皮层后HC饮食。此外，与WT小鼠相比，ND时apoE KO小鼠中存在显著的星形胶质细胞活化。长期暴露于HC饮食和apoE缺乏导致脑中NQO 1表达的协同效应。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Hypercholesterolemia has been suggested as a risk factor for Alzheimer's disease (AD). A genetic risk factor for AD is the E4 allele of apolipoprotein E (apoE). ApoE is the major lipoprotein transporter in the brain, and is mainly produced by glial cells. The present study is focussed on analysing the effects of high cholesterol (HC) diet, duration 9 months, on glial activation in the brain, both in wild type (WT) mice and in mice with a null mutation in the apoE gene (knock-out, KO) mice. The activation of astrocytes and microglia was analysed after inummohistochemical labelling of glial fibrillary acidic protein (GFAP), and F4/80, respectively. In addition, the expression of the antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) was analysed. There was a marked stimulation of astrocyte and microglial activation as well as induced expression of NQO1 in the hippocampus and cerebral cortex upon HC diet. Furthermore, there was significant astrocyte activation in the apoE KO mice, as compared to the WT mice, on ND. The long time exposure to HC diet combined with apoE deficiency resulted in a synergistic effect on the expression of NQO1 in the brain. (C) 2004 Elsevier Ireland Ltd. All rights reserved.