Neuroanatomical abnormalities in behaviorally characterized AppV717F transgenic mice
Neuroanatomical abnormalities in behaviorally characterized AppV717F transgenic mice
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DOI：
10.1006/nbdi.1999.0278
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发表时间：
2000-04-01
影响因子：
6.1
通讯作者：
Ungerer, A
中科院分区：
文献类型：
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作者：
Dodart, JC;Mathis, C;Ungerer, A
对先前在一系列行为测试中研究的App（V717 F）转基因（Tg）小鼠的脑进行组织学分析。我们在这里描述的区域和年龄依赖性淀粉样蛋白沉积在杂合子和纯合子Tg小鼠。我们还报告说，Tg小鼠表现出显着的和年龄依赖性的突触密度的突触素免疫反应性测量的变化。令人惊讶的是，早在Tg小鼠3个月大时就观察到相当显著的海马萎缩（20-40%）。统计分析表明，物体识别记忆的缺陷与特定脑区淀粉样蛋白沉积的数量有关，而空间参考和工作记忆的缺陷与突触密度和海马萎缩的变化有关。我们的研究表明，在Tg小鼠中观察到的行为缺陷仅部分与淀粉样蛋白沉积有关，但也与继发于App（V717 F）转基因过表达的神经解剖学改变有关，并且与淀粉样蛋白沉积无关。(C)北京：科学出版社.
Histological analyses were performed on the brains of App(V717F) transgenic (Tg) mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the App(V717F) transgene and independent of amyloid deposition. (C) 2000 Academia Press.