Stover Kurt R, Campbell Mackenzie A, Van Winssen Christine M, Brown Richard E
Department of Psychology and Neuroscience, Dalhousie University, PO Box 1500, Halifax, NS B3H 4R2, Canada.
Department of Psychology and Neuroscience, Dalhousie University, PO Box 1500, Halifax, NS B3H 4R2, Canada.
Behav Brain Res. 2015 Aug 1;289:29-38. doi: 10.1016/j.bbr.2015.04.012. Epub 2015 Apr 17.
Which behavioral test is the most sensitive for detecting cognitive deficits in the 3xTg-AD at 6.5 months of age? The 3xTg-AD mouse model of Alzheimer's disease (AD) has three transgenes (APPswe, PS1M146V, and Tau P301L) which cause the development of amyloid beta plaques, neurofibrillary tangles, and cognitive deficits with age. In order to determine which task is the most sensitive in the early detection of cognitive deficits, we compared male and female 3xTg-AD and B6129SF2 wildtype mice at 6.5 months of age on a test battery including spontaneous alternation in the Y-Maze, novel object recognition, spatial memory in the Barnes maze, and cued and contextual fear conditioning. The 3xTg-AD mice had impaired learning and memory in the Barnes maze but performed better than B6129SF2 wildtype mice in the Y-Maze and in contextual fear conditioning. Neither genotype demonstrated a preference in the novel object recognition task nor was there a genotype difference in cued fear conditioning but females performed better than males. From our results we conclude that the 3xTg-AD mice have mild cognitive deficits in spatial learning and memory and that the Barnes maze was the most sensitive test for detecting these cognitive deficits in 6.5-month-old mice.
哪种行为测试对检测6.5月龄3xTg-AD小鼠的认知缺陷最为敏感？阿尔茨海默病（AD）的3xTg-AD小鼠模型有三个转基因（APPswe、PS1M146V和Tau P301L），这些转基因会随着年龄增长导致β淀粉样蛋白斑块、神经原纤维缠结以及认知缺陷的出现。为了确定哪种测试任务在早期检测认知缺陷方面最为敏感，我们在一系列测试中比较了6.5月龄的雄性和雌性3xTg-AD小鼠以及B6129SF2野生型小鼠，这些测试包括Y迷宫中的自发交替、新物体识别、巴恩斯迷宫中的空间记忆以及线索性和情境性恐惧条件反射。3xTg-AD小鼠在巴恩斯迷宫中的学习和记忆受损，但在Y迷宫和情境性恐惧条件反射测试中的表现优于B6129SF2野生型小鼠。在新物体识别任务中，两种基因型均未表现出偏好，在线索性恐惧条件反射测试中也没有基因型差异，但雌性小鼠的表现优于雄性小鼠。根据我们的结果，我们得出结论，3xTg-AD小鼠在空间学习和记忆方面存在轻度认知缺陷，并且巴恩斯迷宫是检测6.5月龄小鼠这些认知缺陷最为敏感的测试。
