Onset of hippocampus-dependent memory impairments in 5XFAD transgenic mouse model of Alzheimer's disease
Onset of hippocampus-dependent memory impairments in 5XFAD transgenic mouse model of Alzheimer's disease
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DOI：
10.1002/hipo.22267
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发表时间：
2014-07-01
期刊：
影响因子：
3.5
通讯作者：
Marchetti, Evelyne
中科院分区：
文献类型：
--
作者：
Girard, Stephane D.;Jacquet, Marlyse;Marchetti, Evelyne
5XFAD小鼠是一种早发性阿尔茨海默病（AD）转基因模型，其中淀粉样斑块在2至4个月大的皮质层5和海马体形成的下丘中首次被观察到。尽管在这些小鼠中已经描述了认知改变，但没有研究集中在海马体依赖性记忆缺陷的发病上，而海马体依赖性记忆缺陷是阿尔茨海默病前驱阶段的一个标志。为了确定第一次学习和记忆障碍出现的时间，研究人员使用嗅觉管迷宫将2个月、4个月和6个月大的5XFAD小鼠与它们各自的野生型同伴进行了比较。嗅觉管迷宫是一项非常敏感的海马体依赖任务。孩子在4个月时开始出现学习和记忆方面的缺陷，6个月时显著增加，但没有观察到嗅觉障碍。使用磁共振成像对整个大脑和特定区域（嗅球、纹状体和海马体）进行的体积研究没有发现神经解剖上的差异。轻微的记忆缺陷出现在4个月大时，与星形胶质细胞增生和淀粉样斑块形成增加有关。这种与海马功能障碍相关的早期学习和记忆障碍特别适合评估旨在延迟或抑制阿尔茨海默病发病的临床前治疗策略。(c) 2014 Wiley期刊公司
The 5XFAD mice are an early-onset transgenic model of Alzheimer's disease (AD) in which amyloid plaques are first observed between two and four months of age in the cortical layer five and in the subiculum of the hippocampal formation. Although cognitive alterations have been described in these mice, there are no studies that focused on the onset of hippocampus-dependent memory deficits, which are a hallmark of the prodromal stage of AD. To identify when the first learning and memory impairments appear, 5XFAD mice of two, four, and six months of age were compared with their respective wild-type littermates using the olfactory tubing maze, which is a very sensitive hippocampal-dependent task. Deficits in learning and memory started at four months with a substantial increase at six months of age while no olfactory impairments were observed. The volumetric study using magnetic resonance imaging of the whole brain and specific areas (olfactory bulb, striatum, and hippocampus) did not reveal neuro-anatomical difference. Slight memory deficits appeared at 4 months of age in correlation with an increased astrogliosis and amyloid plaque formation. This early impairment in learning and memory related to the hippocampal dysfunction is particularly suited to assess preclinical therapeutic strategies aiming to delay or suppress the onset of AD. (c) 2014 Wiley Periodicals, Inc.