Reversal of presynaptic deficits of apolipoprotein E-deficient mice in human apolipoprotein E transgenic mice

被引:25
作者
Chapman, S
Sabo, T
Roses, AD
Michaelson, DM [1 ]
机构
[1] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel
[2] Glaxo Wellcome Inc, Div Res, Res Triangle Pk, NC 27709 USA
关键词
Alzheimer's disease; apolipoprotein E; transgenic mice; brain; cholinergic; dopaminergic;
D O I
10.1016/S0306-4522(00)00087-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:419 / 424
页数:6
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