Shin Sang-Wook, Kim Dong-Hee, Jeon Won Kyung, Han Jung-Soo
Department of Biological Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea.
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
Biomedicines. 2020 Sep 3;8(9):326. doi: 10.3390/biomedicines8090326.
Oxidative stress was implicated in the functional impairment of the frontal cortex observed in early Alzheimer's disease (AD). To elucidate this role in an animal AD model, we assessed cognitive function of 4-month-old five familial AD (5XFAD) transgenic (Tg) mice using a learning strategy-switching task requiring recruitment of the frontal cortex and measuring levels of 4-hydroxy-2--nonenal (4-HNE), a marker of oxidative stress, in their frontal cortex. Mice were sequentially trained in cued/response and place/spatial versions of the water maze task for four days each. 5XFAD and non-Tg mice exhibited equal performance in cued/response training. However, 5XFAD mice used spatial search strategy less than non-Tg mice in the spatial/place training. Immunoblot and immunofluorescence staining showed that 4-HNE levels increased in the frontal cortex, but not in the hippocampus and striatum, of 5XFAD mice compared to those in non-Tg mice. We report early cognitive deficits related to the frontal cortex and the frontal cortex's oxidative damage in 4-month-old 5XFAD mice. These results suggest that 4-month-old 5XFAD mice be a useful animal model for the early diagnosis and management of AD.
氧化应激与早期阿尔茨海默病（AD）中观察到的额叶皮质功能损害有关。为了在动物AD模型中阐明这一作用，我们使用一种需要额叶皮质参与的学习策略转换任务评估了4个月大的五只家族性AD（5XFAD）转基因（Tg）小鼠的认知功能，并测量了它们额叶皮质中氧化应激标志物4-羟基-2-壬烯醛（4-HNE）的水平。小鼠在水迷宫任务的线索/反应和位置/空间版本中依次接受训练，各训练四天。5XFAD小鼠和非Tg小鼠在线索/反应训练中的表现相当。然而，在空间/位置训练中，5XFAD小鼠比非Tg小鼠更少使用空间搜索策略。免疫印迹和免疫荧光染色显示，与非Tg小鼠相比，5XFAD小鼠额叶皮质中的4-HNE水平升高，而海马体和纹状体中的4-HNE水平未升高。我们报告了4个月大的5XFAD小鼠中与额叶皮质相关的早期认知缺陷以及额叶皮质的氧化损伤。这些结果表明，4个月大的5XFAD小鼠是AD早期诊断和管理的有用动物模型。
