Age-dependent enhancement of hippocampal long-term potentiation in knock-in mice expressing human apolipoprotein E4 instead of mouse apolipoprotein E
Age-dependent enhancement of hippocampal long-term potentiation in knock-in mice expressing human apolipoprotein E4 instead of mouse apolipoprotein E
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DOI：
10.1016/j.neulet.2004.07.084
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发表时间：
2004-10-21
影响因子：
2.5
通讯作者：
Nukina, N
中科院分区：
文献类型：
--
作者：
Kitamura, HW;Hamanaka, H;Nukina, N
人载脂蛋白E（apoE）包括apoE 2、apoE 3和apoE 4，apoE 4是阿尔茨海默病（AD）的危险因子。AD的临床症状之一是记忆障碍，其已被认为与突触可塑性如长时程增强（UP）有关。在这里，我们显示了在年轻时，在敲入小鼠缺乏小鼠apoE，而是表达人类apoE4的海马UP的增强。在apoE4基因敲入小鼠中UP的增强是年龄依赖性的，并且在成年apoE4基因敲入小鼠中UP的增强消失。在apoE3基因敲入的小鼠中，UP是不变的，因此人apoE4，而不是apoE3，在年轻时特异性地调节突触可塑性。由于基础突触传递和谷氨酸受体的分布，以及突触前功能，是完整的apoE4基因敲入小鼠，突触后功能的修改，通过脂质稳态的UP建议。ApoE4基因敲入小鼠将是一个有用的人类apoE4携带者的动物模型，我们的发现，UP在年轻的apoE4基因敲入小鼠中增强与先前的报告显示年轻的人类apoE4携带者具有更高的智力雅阁。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Human apolipoprotein E (apoE) comprises three isoforms, apoE2, apoE3 and apoE4, and apoE4 has been reported as a risk factor of Alzheimer's disease (AD). One of the clinical symptoms of AD is disorder of memory that has been suggested to be related with synaptic plasticity such as long-term potentiation (UP). Here, we show the enhancement of hippocampal UP at younger age in knock-in mice lacking mouse apoE, but instead expressing human apoE4. The enhancement of UP in apoE4 knock-in mice is age-dependent, and it disappears in adult apoE4 knock-in mice. In apoE3 knock-in mice UP is unaltered, thus human apoE4, but not apoE3, specifically modulates synaptic plasticity at younger age. Since basal synaptic transmission and distribution of glutamate receptors, as well as presynaptic functions, are intact in apoE4 knock-in mice, postsynaptic functional modification of UP through lipid homeostasis is suggested. ApoE4 knock-in mice would be a useful animal model of human apoE4 carriers, and our finding that UP is enhanced in younger apoE4 knock-in mice is in accord with the previous report showing higher intelligence in young human apoE4 carriers. (C) 2004 Elsevier Ireland Ltd. All rights reserved.