Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
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DOI：
10.1038/6374
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发表时间：
1999-03-01
影响因子：
25
通讯作者：
Hsiao, KK
中科院分区：
文献类型：
--
作者：
Chapman, PF;White, GL;Hsiao, KK
我们研究了过度表达突变的695-氨基酸人类淀粉样前体蛋白（APP（695）SWE）的小鼠海马切片中的突触通讯和可塑性，这些小鼠表现出模拟阿尔茨海默病的行为和组织病理学异常。尽管老年APP转基因小鼠表现出正常的快速突触传递和短期可塑性，但它们在海马CA 1和齿状回区域的体外和体内长时程增强（LTP）严重受损。在老年转基因者中，LTP缺陷与空间工作记忆任务中的表现受损相关。这些赤字伴随着最小或没有损失的突触前或突触后的基本结构元件在海马，这表明功能性突触可塑性的损害可能是这些小鼠的认知缺陷，并可能在阿尔茨海默氏症患者的基础。
We investigated synaptic communication and plasticity in hippocampal slices from mice overexpressing mutated 695-amino-acid human amyloid precursor protein (APP(695)SWE), which show behavioral and histopathological abnormalities simulating Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast synaptic transmission and short term plasticity, they are severely impaired in in-vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus regions of the hippocampus. The LTP deficit was correlated with impaired performance in a spatial working memory task in aged transgenics. These deficits are accompanied by minimal or no loss of presynaptic or postsynaptic elementary structural elements in the hippocampus, suggesting that impairments in functional synaptic plasticity may underlie some of the cognitive deficits in these mice and, possibly, in Alzheimer's patients.