Schneider F, Baldauf K, Wetzel W, Reymann K G
German Centre for Neurodegenerative Diseases (DZNE), D-39120 Magdeburg, Germany.
Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany.
Physiol Behav. 2014 Aug;135:25-33. doi: 10.1016/j.physbeh.2014.05.041. Epub 2014 Jun 4.
Transgenic animal models of Alzheimer's disease (AD) are widely used to investigate mechanisms of pathophysiology and cognitive dysfunctions. A model with a very early development of parenchymal plaque load at the age of 2months is the 5xFAD mouse (Tg6799, Oakley et al. 2006). These 5xFAD mice over-express both human amyloid precursor protein (APP) and human presenilin 1 (PS1). Mice from this line have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β (Aβ). The aim of this study was the behavioral and functional investigations of 5xFAD males because in most studies females of this strain were characterized. In comparison to literature of transgenic 5xFAD females, transgenic 5xFAD males showed decreased anxiety in the elevated plus maze, reduced locomotion and exploration in the open field and disturbances in learning performance in the Morris water maze starting at 9months of age. Electroencephalogram (EEG) recordings on 6month old transgenic mice revealed a decrease of delta, theta, alpha, beta and gamma frequency bands whereas the subdelta frequency was increased. EEG recordings during sleep showed a reduction of rapid eye movement sleep in relation to the amount of total sleep. Thus, 5xFAD males develop early functional disturbances and subsequently behavioral deficits and therefore they are a good mouse model for studying Alzheimer's disease.
阿尔茨海默病(AD)转基因动物模型被广泛用于研究病理生理学机制和认知功能障碍。5xFAD小鼠(Tg6799,Oakley等人,2006年)是一种在2个月大时实质斑块负荷就很早出现的模型。这些5xFAD小鼠同时过度表达人类淀粉样前体蛋白(APP)和人类早老素1(PS1)。该品系的小鼠具有高APP表达,这与淀粉样β蛋白(Aβ)42个氨基酸种类的高负荷和加速积累相关。本研究的目的是对5xFAD雄性小鼠进行行为和功能研究,因为在大多数研究中该品系的雌性小鼠已被表征。与转基因5xFAD雌性小鼠的文献相比,转基因5xFAD雄性小鼠在高架十字迷宫中焦虑减少,在旷场试验中运动和探索减少,并且从9个月大开始在莫里斯水迷宫中的学习表现出现障碍。对6个月大的转基因小鼠进行脑电图(EEG)记录显示,δ、θ、α、β和γ频段减少,而亚δ频段增加。睡眠期间的EEG记录显示,快速眼动睡眠相对于总睡眠时间减少。因此,5xFAD雄性小鼠早期出现功能障碍,随后出现行为缺陷,因此它们是研究阿尔茨海默病的良好小鼠模型。