No evidence for cholinergic problems in apolipoprotein E knockout and apolipoprotein E4 transgenic mice
No evidence for cholinergic problems in apolipoprotein E knockout and apolipoprotein E4 transgenic mice
复制标题
DOI：
10.1016/s0306-4522(00)00016-6
复制
发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
Van Leuven, F
中科院分区：
文献类型：
--
作者：
Bronfman, FC;Tesseur, I;Van Leuven, F
载脂蛋白E基因的epsilon 4等位基因是阿尔茨海默病的主要遗传危险因素。这种蛋白质是否以及如何导致阿尔茨海默病的病理级联尚不清楚。epsilon 4等位基因特别影响胆碱能缺陷，这是阿尔茨海默病患者大脑中最常见的神经递质问题之一。我们分析了载脂蛋白E敲除小鼠和过表达人载脂蛋白E4的转基因小鼠脑胆碱能系统的几个参数。我们分析了不同脑区胆碱能纤维的分布、胆碱能神经元的数量和形态以及乙酰胆碱酯酶和胆碱乙酰转移酶的活性。最后，我们分析了高亲和力胆碱转运体的特异性标记物[H-3] -3在脑不同部位和区域的分布和结合参数。与年龄匹配的非转基因小鼠相比，在载脂蛋白E4转基因小鼠或载脂蛋白E敲除小鼠中，这项广泛的努力未能显示所研究的胆碱能参数有任何一致的差异。我们得出结论，载脂蛋白E4本身对小鼠脑胆碱能系统无害。(c) 2000 ibro。Elsevier Science Ltd.出版。
The epsilon 4 allele of the apolipoprotein E gene constitutes the major genetic risk factor to develop Alzheimer's disease. If and how this protein contributes to the pathological cascade of Alzheimer's disease is not known. The epsilon 4 allele particularly affects the cholinergic defect, which is one of the most consistent neurotransmitter problems in an Alzheimer's disease brain.We have analysed several parameters of the cholinergic system in brain of apolipoprotein E knockout mice as well as in transgenic mice overexpressing human apolipoprotein E4. We analysed the distribution of cholinergic fibers, the number and morphology of cholinergic neurons and the enzymatic activity of acetylcholinesterase and choline acetyltransferase in different brain regions. Finally, we analysed the distribution and the binding parameters of [H-3]hemicholinium-3, a specific marker for the high affinity choline transporter in different brain sections and regions.This extensive effort failed to show any consistent difference in the cholinergic parameters studied, in either the apolipoprotein E4 transgenic mice or in the apolipoprotein E knockout mice, compared to age-matched non-transgenic mice. We conclude that the apolipoprotein E4 is not deleterious per se for the cholinergic system in mouse brain. (C) 2000 IBRO. Published by Elsevier Science Ltd.