REST/NRSF-induced changes of ChAT protein expression in the neocortex and hippocampus of the 3xTg-AD mouse model for Alzheimer's disease
REST/NRSF-induced changes of ChAT protein expression in the neocortex and hippocampus of the 3xTg-AD mouse model for Alzheimer's disease
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DOI：
10.1016/j.lfs.2014.09.013
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发表时间：
2014-10-29
期刊：
影响因子：
6.1
通讯作者：
Diaz-Cintra, S.
中科院分区：
文献类型：
--
作者：
Orta-Salazar, E.;Aguilar-Vazquez, A.;Diaz-Cintra, S.
目的：胆碱能系统是阿尔茨海默病 (AD) 中发生改变的神经递质系统之一，阿尔茨海默病是人类痴呆症最常见的形式。这项工作的目的是确定 REST/NRSF 参与 AD 转基因小鼠（纯合 3xTg-AD）新皮质和海马 ChAT 表达的改变，该转基因小鼠过表达 3 种蛋白：淀粉样蛋白-β 前体蛋白、早老素-1 和 tau，所有这些蛋白都与 AD 相关并导致细胞变性。主要方法：两组（WT 和 3xTg-AD），11 个月大对雌性小鼠进行了分析和比较。每组的一半大脑用于 ChAT 免疫组织化学，另一半进行 ChAT 和 REST/NRSF 的蛋白质印迹分析。 主要发现：与对照小鼠相比，我们观察到转基因小鼠 Meynert 核中的 ChAT 免疫反应细胞数量以及额叶运动皮层和海马 CA1 区的纤维数量显着减少。与对照组相比，3xTg-AD 小鼠后两个大脑区域的 REST/NRSF 蛋白表达水平升高，ChAT 蛋白表达降低。这些发现可能与 AD 中观察到的退化有关。 (C) 2014 Elsevier Inc. 保留所有权利。
Aims: The cholinergic system is one of the neurotransmitter systems altered in Alzheimer's disease (AD), the most common form of human dementia. The objective of this work was to determine the REST/NRSF involvement in altered ChAT expression in the neocortex and hippocampus of an AD transgenic mouse (homozygous 3xTg-AD) that over-expresses 3 proteins, amyloid-beta precursor protein, presenilin-1, and tau, all of which are associated with AD and cause cellular degeneration.Main methods: Two groups (WT and 3xTg-AD) of 11-month-old female mice were analyzed and compared. Half of the brains of each group were used for ChAT immunohistochemistry, and Western Blot analyses of ChAT and REST/NRSF were performed on the other half.Key findings: We observed significant decreases in the number of ChAT-immunoreactive cells in the Meynert nucleus and of fibers in the frontal motor cortex and hippocampal CA1 area in transgenic mice compared with control mice. An increased level of REST/NRSF protein and a reduction of ChAT protein expression in the 3xTg-AD mice compared with their controls were also found in both in the latter two cerebral regions.Significance: The increased REST/NRSF expression reported here and its effect on the regulatory region for ChAT transcription could explain the decreased expression of ChAT in the 3xTg-AD mouse; these findings may be associated with the degeneration observed in AD. (C) 2014 Elsevier Inc. All rights reserved.