Levi Ofir, Jongen-Relo Ana L, Feldon Joram, Michaelson Daniel M
The Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
J Neurol Sci. 2005 Mar 15;229-230:241-8. doi: 10.1016/j.jns.2004.11.035. Epub 2005 Jan 11.
The allele E4 of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor of Alzheimer's disease (AD), inhibits the improvements in learning and memory which result from exposure of apoE transgenic mice to environmental stimulation (ES). In the present study, we investigated the extent to which these cognitive deficits are associated with distinct presynaptic, postsynaptic and axonal impairments and whether these effects are brain area-specific. Exposure to an enriched environment of young mice transgenic for human apoE3, which is the AD benign apoE allele, increased the levels of the presynaptic protein synaptophysin and of the dendritic marker MAP-2 in the hippocampus and entorhinal cortex, whereas the corresponding levels of these proteins in the apoE4 transgenic mice were unaffected by the enriched environment. In contrast, the levels of synaptophysin and MAP-2 in the motor cortex were elevated by environmental stimulation in both the apoE3 and the apoE4 transgenic mice. These findings show that apoE4 inhibits synaptic plasticity following environmental stimulation and that this effect is both isoform- and brain area-specific.
载脂蛋白E4（apoE4）的E4等位基因是阿尔茨海默病（AD）最常见的遗传风险因素，它会抑制apoE转基因小鼠暴露于环境刺激（ES）后学习和记忆能力的改善。在本研究中，我们调查了这些认知缺陷与不同的突触前、突触后和轴突损伤的关联程度，以及这些影响是否具有脑区特异性。暴露于丰富环境中的携带人类apoE3（AD良性apoE等位基因）的转基因幼鼠，海马体和内嗅皮质中突触前蛋白突触素和树突标记物MAP-2的水平升高，而apoE4转基因小鼠中这些蛋白质的相应水平不受丰富环境的影响。相反，在apoE3和apoE4转基因小鼠中，环境刺激均使运动皮质中突触素和MAP-2的水平升高。这些发现表明，apoE4会抑制环境刺激后的突触可塑性，且这种效应具有异构体和脑区特异性。
