阿尔茨海默病的5XFAD小鼠模型显示出对新环境适应的年龄依赖性缺陷

IF 1.7 Q3 CLINICAL NEUROLOGY Aging brain Pub Date : 2023-01-01 DOI:10.1016/j.nbas.2023.100078
Sabrina Smith , Sarah C. Hopp
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摘要

习惯化是一种学习形式,其特征是对重复或延长的刺激反应减弱。在啮齿类动物中,适应新环境的特征是在新环境中度过的时间会减少运动。对新环境的习惯化依赖于海马功能,这表明习惯化行为可能是阿尔茨海默病(AD)特有的海马依赖性记忆缺陷的相关读数。目前在AD临床前动物模型中测量海马依赖性记忆的测定方法尚未准确预测人类试验中新型干预措施的认知保护作用。在这里,我们测试了行为习惯化范式是否可以检测AD样淀粉样蛋白病理的常见临床前小鼠模型5XFAD小鼠中与年龄相关的变化。我们在3个月、6个月和9个月大时将5XFAD小鼠和年龄匹配的野生型(WT)同窝出生的小鼠暴露在一个新的环境中,持续两次,间隔24小时,并测量它们的运动。WT小鼠随着时间的推移习惯于新环境,而5XFAD小鼠在行为习惯化方面表现出年龄依赖性缺陷。我们使用来自5XFAD和具有TREM2*R47H和APOE4突变的晚发性AD小鼠模型的公开可用的开放域数据复制了我们的结果。总的来说,我们提出行为习惯化是一项潜在的敏感任务,用于评估5XFAD小鼠和其他AD小鼠模型中与年龄相关的行为缺陷,可用于测试新型AD疗法的临床前疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The 5XFAD mouse model of Alzheimer’s disease displays age-dependent deficits in habituation to a novel environment

Habituation is a form of learning characterized by a decrement in responsiveness to a stimulus that is repeated or prolonged. In rodents, habituation to a novel environment is characterized by a decrease in locomotion over time spent in a novel environment. Habituation to a novel environment is dependent on hippocampal function, suggesting that habituation behavior may be a relevant readout for hippocampal-dependent memory deficits that are characteristic of Alzheimer’s disease (AD). Current assays that measure hippocampal-dependent memory in preclinical animal models of AD have not accurately predicted the cognitive protection of novel interventions in human trials. Here, we tested whether a behavioral habituation paradigm could detect age-associated changes in a common preclinical mouse model of AD-like amyloid pathology, the 5XFAD mouse. We exposed 5XFAD mice and age-matched wild-type (WT) littermates at 3, 6, and 9 months of age to a novel environment over two sessions separated by 24 h and measured their locomotion. WT mice habituated to the novel environment over time, while 5XFAD mice displayed age-dependent deficits in behavioral habituation. We replicated our results using publicly available open field data from 5XFAD and late-onset AD mouse models with TREM2*R47H and APOE4 mutations. Overall, we present behavioral habituation as a potentially sensitive task to assess age-associated behavioral deficits in 5XFAD mice and other mouse models of AD that could be used to test the preclinical efficacy of novel AD therapeutics.

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Aging brain
Aging brain Neuroscience (General), Geriatrics and Gerontology
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