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阿尔茨海默病转基因淀粉样前体蛋白小鼠模型的空间学习和记忆损伤以及运动增加。

Spatial learning and memory impairment and increased locomotion in a transgenic amyloid precursor protein mouse model of Alzheimer's disease.

机构信息

Department of Psychological Sciences, 210 McAlester Hall, University of Missouri, Columbia, MO 65211, USA.

出版信息

Behav Brain Res. 2011 Sep 12;222(1):169-75. doi: 10.1016/j.bbr.2011.03.049. Epub 2011 Apr 1.

DOI:10.1016/j.bbr.2011.03.049
PMID:21443906
Abstract

This study provides an examination of spatial learning and a behavioral assessment of irritability and locomotion in TgCRND8 mice, an amyloid precursor protein transgenic model of Alzheimer's disease. Performance was assessed using the Barnes maze, the touch escape test, and an open-field test. While past research focused primarily on 2-5-month-old TgCRND8 mice, the present study used an older age cohort (9-month-old female mice), in addition to a 4-month-old cohort of both transgenic (Tg) and wildtype female mice. Both younger and older Tg mice displayed poor spatial learning in the Barnes maze task compared to their wildtype littermates, as demonstrated by significantly longer latencies and more errors both during acquisition and at a 2-week retest. No differences in irritability were found between Tg and control mice in the younger cohort; however, older Tg mice displayed significantly higher irritability compared with wildtype littermates, as measured by the touch escape test. Additionally, Tg mice of both age cohorts showed increased locomotion and slowed habituation during a 60-min open-field test over 3 days of testing. These results demonstrate that TgCRND8 mice show significant deficits in spatial and nonspatial behavioral tasks at advanced stages of amyloid pathology.

摘要

本研究对 TgCRND8 小鼠(阿尔茨海默病的淀粉样前体蛋白转基因模型)的空间学习和易激惹行为以及运动行为进行了检查。使用 Barnes 迷宫、触碰逃避测试和旷场测试进行了行为评估。虽然过去的研究主要集中在 2-5 月龄的 TgCRND8 小鼠上,但本研究使用了年龄更大的队列(9 月龄雌性小鼠),以及 4 月龄的转基因(Tg)和野生型雌性小鼠队列。与野生型同窝小鼠相比,年轻和年老的 Tg 小鼠在 Barnes 迷宫任务中的空间学习表现都较差,表现在获得阶段和 2 周后的重测中潜伏期明显延长且错误明显增多。在年轻队列中,Tg 和对照小鼠之间没有发现易激惹行为的差异;然而,与野生型同窝小鼠相比,年老的 Tg 小鼠的易激惹行为明显更高,这通过触碰逃避测试来衡量。此外,两个年龄组的 Tg 小鼠在 3 天的测试中,在旷场测试的 60 分钟内表现出运动增加和习惯化速度减慢。这些结果表明,TgCRND8 小鼠在淀粉样蛋白病理的晚期表现出明显的空间和非空间行为任务缺陷。

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