Reversal of presynaptic deficits of apolipoprotein E-deficient mice in human apolipoprotein E transgenic mice
Reversal of presynaptic deficits of apolipoprotein E-deficient mice in human apolipoprotein E transgenic mice
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DOI：
10.1016/s0306-4522(00)00087-7
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发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
Michaelson, DM
中科院分区：
文献类型：
--
作者：
Chapman, S;Sabo, T;Michaelson, DM
载脂蛋白E基因型是阿尔茨海默病的一个重要危险因素，与不同脑神经系统的变性有关。在本研究中，我们采用载脂蛋白E缺陷小鼠和人载脂蛋白E3和载脂蛋白E4转基因小鼠空小鼠载脂蛋白E的背景下，检查在何种程度上不同的脑神经元系统的影响载脂蛋白E和这种效果的亚型特异性。利用神经元特异性突触前标记物进行组织学和放射自显影测量。由此获得的结果显示，年轻的载脂蛋白E缺陷小鼠的脑胆碱能和去甲肾上腺素能神经末梢的水平显着降低，脑多巴胺能神经末梢没有变化。这些胆碱能和去甲肾上腺素能突触前紊乱在人载脂蛋白E3和载脂蛋白E4转基因小鼠中得到类似的改善。在胆碱能系统的情况下，这导致突触前赤字的完全逆转，而在去甲肾上腺素能神经元的情况下，改善是partial.These研究结果表明，脑胆碱能和去甲肾上腺素能神经元显着更依赖于脑载脂蛋白E比脑多巴胺能神经元，这些影响的亚型特异性是不明显的，在年轻的年龄在非挑战条件下。(C)2000 IBRO。出版社：Elsevier Science Ltd
Apolipoprotein E genotype is an important risk factor of Alzheimer's disease, which is associated with the degeneration of distinct brain neuronal systems. In the present study we employed apolipoprotein E-deficient mice and human apolipoprotein E3 and apolipoprotein E4 transgenic mice on a null mouse apolipoprotein E background, to examine the extent to which distinct brain neuronal systems are affected by apolipoprotein E and the isoform specificity of this effect. This was pursued by histological and autoradiographic measurements utilizing neuron specific presynaptic markers. The results thus obtained revealed significant reductions in the levels of brain cholinergic and noradrenergic nerve terminals in young apolipoprotein E-deficient mice and no changes in brain dopaminergic nerve terminals. These cholinergic and noradrenergic presynaptic derangements were ameliorated similarly in human apolipoprotein E3 and apolipoprotein E4 transgenic mice. In the case of the cholinergic system, this resulted in complete reversal of the presynaptic deficits, whereas in the case of the noradrenergic neurons the amelioration was partial.These findings suggest that brain cholinergic and noradrenergic neurons are markedly more dependent on brain apolipoprotein E than brain dopaminergic neurons and that the isoform specificity of these effects is not apparent at a young age under non-challenged conditions. (C) 2000 IBRO. Published by Elsevier Science Ltd.