Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer's disease.
Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer's disease.
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DOI：
10.1186/alzrt182
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Van Eldik LJ
中科院分区：
文献类型：
--
作者：
Webster SJ;Bachstetter AD;Van Eldik LJ
尽管淀粉样蛋白前体蛋白(APP)/早老素-1 （PS-1）敲入小鼠阿尔茨海默病（AD）模型具有广泛的机制和病理特征，但对该模型中AD相关的行为缺陷知之甚少。在各种功能任务中的基线行为表现的特征和行为障碍的时间起病的识别对于为未来阿尔茨海默病治疗的临床前测试提供基础至关重要。在这里，我们对该模型进行了全面的行为表征，讨论了观察到的行为如何与他人的机制和病理观察相关联，并将该模型与其他常用的AD小鼠模型进行了比较。在该模型的整个生命周期内，四组不同的小鼠（实验组：7、11、15和24个月大）在行为测试组中运行，包括评估运动功能的任务（握力、转子杆、梁行走、开阔场地走动）、焦虑相关行为（开阔场地在外围区与中心区度过的时间、升高加迷宫）和认知功能（新物体识别、径向臂水迷宫）。APP/PS-1敲入小鼠与野生型小鼠在任何年龄组的运动功能或焦虑相关行为均无差异。随着疾病的进展，敲入小鼠在识别记忆（新物体识别）和空间参考记忆（径向臂水迷宫）方面的认知缺陷变得明显。这是首次报道的APP/PS1敲入小鼠AD模型的综合行为学分析。缺乏运动/协调缺陷或异常焦虑水平，加上年龄/疾病相关的认知能力下降以及该模型的高生理相关性，使其非常适合用于ad相关治疗的临床前测试。
Despite the extensive mechanistic and pathological characterization of the amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model of Alzheimer's disease (AD), very little is known about the AD-relevant behavioral deficits in this model. Characterization of the baseline behavioral performance in a variety of functional tasks and identification of the temporal onset of behavioral impairments are important to provide a foundation for future preclinical testing of AD therapeutics. Here we perform a comprehensive behavioral characterization of this model, discuss how the observed behavior correlates with the mechanistic and pathological observations of others, and compare this model with other commonly used AD mouse models. Four different groups of mice ranging across the lifespan of this model (test groups: 7, 11, 15, and 24 months old) were run in a behavioral test battery consisting of tasks to assess motor function (grip strength, rotor rod, beam walk, open field ambulatory movement), anxiety-related behavior (open field time spent in peripheral zone vs. center zone, elevated plus maze), and cognitive function (novel object recognition, radial arm water maze). There were no differences in motor function or anxiety-related behavior between APP/PS-1 knock-in mice and wild-type counterpart mice for any age group. Cognitive deficits in both recognition memory (novel object recognition) and spatial reference memory (radial arm water maze) became apparent for the knock-in animals as the disease progressed. This is the first reported comprehensive behavioral analysis of the APP/PS1 knock-in mouse model of AD. The lack of motor/coordination deficits or abnormal anxiety levels, coupled with the age/disease-related cognitive decline and high physiological relevance of this model, make it well suited for utilization in preclinical testing of AD-relevant therapeutics.
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影响因子：
64.8
作者：
Chen, GQ;Chen, KS;Morris, RGM
通讯作者：
Morris, RGM
影响因子：
4.8
作者：
Davis, J;Xu, F;Van Nostrand, WE
通讯作者：
Van Nostrand, WE
影响因子：
2
作者：
Daumas, Stephanie;Sandin, Johan;Morris, Richard G. M.
通讯作者：
Morris, Richard G. M.
影响因子：
4.2
作者：
Ambree, Oliver;Richter, Helene;Schaebitz, Wolf-Ruediger
通讯作者：
Schaebitz, Wolf-Ruediger
影响因子：
5.3
作者：
Carroll, Jenna C.;Rosario, Emily R.;Pike, Christian J.
通讯作者：
Pike, Christian J.