Absence of central cholinergic deficits in ApoE knockout mice
Absence of central cholinergic deficits in ApoE knockout mice
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DOI：
10.1007/s002130050329
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发表时间：
1997-07-01
影响因子：
3.4
通讯作者：
Higgins, GA
中科院分区：
文献类型：
--
作者：
Anderson, R;Higgins, GA
载脂蛋白E（ApoE）基因型是阿尔茨海默病（Alzheimer's disease，AD）的主要危险因素，但ApoE亚型影响AD的机制尚不清楚。最近的研究表明，小鼠缺乏ApoE可能表现出受损的中枢胆碱能功能。由于该神经递质系统传统上与AD的发病机制有关，我们进一步研究了ApoE基因缺失对该系统的影响。使用一系列行为、生物化学和组织化学技术，将12月龄雌性ApoE敲除（ko）小鼠与野生型同窝对照小鼠进行比较。用拟胆碱药多奈哌齐（E2020; 2.5-5 mg kg（-1）IF）预处理，在野生型和ApoE ko小鼠中均产生显著的体温降低和震颤诱导。两组之间的变化幅度没有显著差异。在Morris水迷宫中的认知测试显示，野生型和ApoE ko小鼠都可以以相似的获取率和准确性学习隐藏的逃避平台的位置。同样，两种基因型的行为证明在Y-迷宫自发交替过程中是不可区分的。用于两种认知测试的方案然后被证明是敏感的东莨菪碱（但不是甲基溴化东莨菪碱）的破坏性影响。行为测试后，胆碱乙酰转移酶（ChAT）的活性在海马，额叶和内嗅皮层和纹状体。在每种情况下，基因型之间没有差异。此外，冠状面的纹状体和前海马区的ApoE ko和野生型小鼠显示类似的模式的乙酰胆碱酯酶（AChE）染色，没有定性或明显的定量差异。最后，血浆胆固醇水平分析证实了ApoE基因型。总之，使用的行为，组织化学和生化测量的组合，我们没有检测到任何显着差异，野生型和ApoE ko小鼠之间的中枢胆碱能活性。
ApolipoproteinE (ApoE) genotype has recently been identified as a major risk factor for Alzheimer's disease (AD) but the mechanism(s) by which ApoE isoforms influence this disease remain unclear. Recent studies suggest that mice deficient in ApoE may exhibit impaired central cholinergic function. Since this neurotransmitter system has traditionally been associated with the pathogenesis of AD, we have further investigated the impact of ApoE gene deletion on this system. Female ApoE knockout (ko) mice, age 12 months, were compared with wild type littermate controls using a range of behavioural, biochemical and histochemical techniques. Pre-treatment with the cholinomimetic, donepezil (E2020; 2.5-5 mg kg(-1) IF), produced significant hypothermia and induction of tremor in both wild type and ApoE ko mice. The magnitude of change did not significantly differ between the groups. Cognitive testing in the Morris water maze revealed that both wild type and ApoE ko mice could learn the location of a hidden escape platform with similar rates of acquisition and accuracy. Similarly, the behaviour of both genotypes proved indistinguishable in a Y-maze spontaneous alternation procedure. The protocols used for both cognitive tests were then shown to be sensitive to the disruptive effects of scopolamine (but not scopolamine methyl bromide). Following behavioural testing, choline acetyltransferase (ChAT) activity was measured in the hippocampus, frontal and entorhinal cortex and striatum. In each case there was no difference between the genotypes. In addition, coronal sections of striatum and anterior hippocampal regions of ApoE ko and wild type mice showed similar patterns of acetylcholinesterase (AChE) staining, with no qualitative or obvious quantitative difference. Finally, analysis of plasma cholesterol levels confirmed ApoE genotype. In conclusion, using a combination of behavioural, histochemical and biochemical measurements, we have failed to detect any significant differences in central cholinergic activity between wild type and ApoE ko mice.