Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice
Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice
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DOI：
10.1007/s11357-016-9929-7
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发表时间：
2016-08-01
期刊：
影响因子：
--
通讯作者：
Xiao, Ming
中科院分区：
文献类型：
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作者：
Huang, Huang;Nie, Sipei;Xiao, Ming
过量产生淀粉样β蛋白(Aβ)的APPswe/PS1dE9(APP/PS1)转基因小鼠被广泛应用于阿尔茨海默病(AD)的发病机制研究、实验治疗和新药筛选。然而，目前的大多数文献使用的是年轻或成年的APP/PS1小鼠。为了对该动物模型的AD样表型提供更广泛的认识，本研究系统地分析了24月龄雄性APP/PS1小鼠的行为和病理学特征。老年APP/PS1小鼠存在参考记忆缺陷以及焦虑、多动和社会互动障碍。一直以来，在背侧海马区有明显的淀粉样斑块沉积，胰岛素降解酶的表达减少，这是一种负责降解细胞内Aβ的蛋白水解酶。此外，老年APP/PS1小鼠的海马体体积、神经元数量和突触素表达减少，星形胶质细胞萎缩。这一发现表明，老年APP/PS1小鼠可以很好地复制AD患者的认知和非认知行为异常、海马萎缩以及神经元和星形胶质细胞变性，从而能够更客观和更精细地对AD治疗药物和治疗策略进行临床前评估。
Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (A beta) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular A beta. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.