Behavioral characterization of the Tg2576 transgenic model of Alzheimer's disease through 19 months
Behavioral characterization of the Tg2576 transgenic model of Alzheimer's disease through 19 months
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DOI：
10.1016/s0031-9384(02)00639-x
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发表时间：
2002-04-15
影响因子：
2.9
通讯作者：
Arendash, GW
中科院分区：
文献类型：
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作者：
King, DL;Arendash, GW
阿尔茨海默病(AD)转基因模型在衰老过程中的多个时间点的行为特征在很大程度上是不充分的，通常限于一到两个基于认知的任务，在这种背景下，本研究利用综合的6周行为电池来表征Tg2576 AD转基因(TG(+))、小鼠和非转基因(TG(-))对照3、9、14和19个月的感觉运动和认知表现。在所有四个时间点上，与TG小鼠相比，TG(+)小鼠在Y迷宫自发交替、可见平台识别和几个感觉运动任务中都受到了损害；TG(+)小鼠的活动测量也总体上增加了。可见平台缺陷在9个月龄时明显，而感觉运动任务的缺陷在14个月龄时明显。虽然Tg(+)小鼠表现出的行为损害通常在19个月期间是进行性的，但Tg(-)小鼠在相同的行为测量中也表现出类似的进行性下降；因此，没有任务显示只有Tg(+)小鼠的进行性行为下降。此外，尽管6周的行为组合包括6个基于认知的任务(即Y迷宫、可见平台、Morris水迷宫、圆形平台、被动回避和主动回避)，但19个月的行为分析显示，TG(+)小鼠仅在Y迷宫和可见平台任务中受损。因此，Tg2576小鼠即使到了老年也不会表现出广泛而深刻的认知障碍。这可能反映了它们的主要C57BL/6背景，以及突变的转基因显然无法深刻改变其中的表现。(C)2002 Elsevier Science Inc.保留所有权利。
Behavioral characterization of Alzheimer's disease (AD) transgenic models over multiple time points during aging has been largely inadequate, usually being limited to one or two cognitive-based tasks, In this context, the present study utilized a comprehensive 6-week behavioral battery to characterize sensorimotor and cognitive performance of Tg2576 AD transgenic (Tg(+)), mice and nontransgenic (Tg(-)) controls aged 3, 9, 14, and 19 months. Compared collectively to Tg- mice over all four time points, Tg(+) mice were impaired in Y-maze spontaneous alternation, visible platform recognition, and several sensorimotor tasks; Tg(+) mice also showed an overall increase in activity measures. The deficits in visible platform became evident by 9 months of age, while those in sensorimotor tasks became clearly manifest by 14 months. Although the behavioral impairments exhibited by Tg(+) mice were usually progressive through 19 months, Tg(-) animals also showed similar progressive decline in the same behavioral measures; thus, no task revealed a progressive behavioral decline exclusive to Tg(+) mice. Moreover, although the 6-week behavioral battery included six cognitively based tasks (i.e., Y-maze, visible platform, Morris water maze, circular platform, passive avoidance, and active avoidance), behavioral analysis through 19 months revealed Tg(+) mice to be impaired in only the Y-maze and visible platform tasks. Consequently, Tg2576 mice do not exhibit widespread, profound cognitive impairment, even into old age. This may reflect their predominant C57BL/6 background and an apparent inability of the mutant transgene to profoundly alter performance therein. (C) 2002 Elsevier Science Inc. All rights reserved.