Cheng David, Low Jac Kee, Logge Warren, Garner Brett, Karl Tim
Neuroscience Research Australia, Randwick, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, NSW 2052, Australia.
Neuroscience Research Australia, Randwick, NSW 2031, Australia; Schizophrenia Research Institute, Darlinghurst, NSW 2010, Australia.
Behav Brain Res. 2014 Mar 1;260:111-8. doi: 10.1016/j.bbr.2013.11.046. Epub 2013 Dec 4.
Murine models are commonly used to evaluate progression of Alzheimer's disease. APPSwe/PS1ΔE9 (APPxPS1) mice have previously been reported to demonstrate impaired learning and memory in the Morris water maze test. However, this paradigm introduces a variety of behaviours that may confound performance of the mice, thus an alternative was sought. A battery of behavioural tests (light-dark test, elevated plus maze, novel object recognition task, social recognition test, cheeseboard task and prepulse inhibition) was used to investigate various behavioural and cognitive domains with relevance to Alzheimer's disease. We found 9-month old female APPxPS1 mice exhibited impaired spatial memory in the reversal cheeseboard task. In addition, task-dependent hyperlocomotion and anxiolytic-like behaviours were observed in the light-dark test. Female APPxPS1 demonstrated intact object recognition memory and sensorimotor gating was not significantly decreased compared to control mice except for one particular interstimulus interval. The social recognition test failed to detect preference for social novelty in control females. In conclusion, this is the first study to describe a memory deficit in female APPxPS1 mice in the hidden cheeseboard task. Transgenic females also exhibited task-dependent reduction in anxiety behaviours and hyperlocomotion. These novel findings enhance our understanding of the behavioural phenotype of APPxPS1 females and present the cheeseboard as a valid alternative to other established spatial memory tests. Furthermore, the task-dependency of some of our findings suggests that behavioural profiling of APPxPS1 transgenic mice should be assessed using a variety of behavioural paradigms.
小鼠模型常用于评估阿尔茨海默病的进展。此前有报道称，APPSwe/PS1ΔE9（APPxPS1）小鼠在莫里斯水迷宫试验中表现出学习和记忆受损。然而，这种范式引入了多种可能混淆小鼠表现的行为，因此寻求了一种替代方法。使用一系列行为测试（明暗测试、高架十字迷宫、新物体识别任务、社会识别测试、棋盘任务和前脉冲抑制）来研究与阿尔茨海默病相关的各种行为和认知领域。我们发现9个月大的雌性APPxPS1小鼠在反向棋盘任务中表现出空间记忆受损。此外，在明暗测试中观察到任务依赖性的活动过度和抗焦虑样行为。雌性APPxPS1表现出完整的物体识别记忆，除了一个特定的刺激间隔外，与对照小鼠相比，感觉运动门控没有显著降低。社会识别测试未能检测到对照雌性对社会新奇性的偏好。总之，这是第一项描述雌性APPxPS1小鼠在隐藏棋盘任务中存在记忆缺陷的研究。转基因雌性小鼠还表现出任务依赖性的焦虑行为减少和活动过度。这些新发现增强了我们对APPxPS1雌性小鼠行为表型的理解，并将棋盘任务作为其他既定空间记忆测试的有效替代方法。此外，我们一些发现的任务依赖性表明，应该使用多种行为范式来评估APPxPS1转基因小鼠的行为特征。
