Hulshof Lianne A, Frajmund Leon A, van Nuijs Danny, van der Heijden Denise C N, Middeldorp Jinte, Hol Elly M
Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands; Department Immunobiology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Neurobiol Aging. 2022 May;113:28-38. doi: 10.1016/j.neurobiolaging.2021.12.009. Epub 2022 Feb 12.
Alzheimer's disease (AD) is the most common cause of dementia. Despite many years of research, very limited treatment options are available. Here we aim to establish a well-defined learning and memory performance test for an AD mouse model, which can be used in future studies to evaluate the effect of novel drugs, treatments, and interventions. We exposed 9-month-old APPswe/PSEN1dE9 mice to a battery of memory tests to determine which test is best suited to study memory deficits in this specific AD mouse model. Since in more recent years it has become clear that there are sex-dependent differences in AD pathology, we also assessed differences in performance between male and female mice. From our test battery, we conclude that the Barnes maze task, which spans multiple days, is better suited to study subtle learning and memory deficits in 9-month-old APPswe/PS1dE9 mice, than the 2 trial T-maze and Fear conditioning task. This test revealed deficits in both spatial memory and cognitive flexibility in the APPswe/PS1dE9 mice compared to wildtype littermates. Furthermore, we conclude that there are no sex dependent memory deficit differences in this AD mouse model at this age.
阿尔茨海默病（AD）是痴呆症最常见的病因。尽管经过多年研究，可用的治疗选择仍然非常有限。在此，我们旨在为AD小鼠模型建立一种明确的学习和记忆性能测试，可用于未来研究以评估新型药物、治疗方法和干预措施的效果。我们将9个月大的APPswe/PSEN1dE9小鼠进行一系列记忆测试，以确定哪种测试最适合研究这种特定AD小鼠模型中的记忆缺陷。由于近年来越来越清楚地认识到AD病理学存在性别差异，我们还评估了雄性和雌性小鼠在性能上的差异。从我们的测试组合中，我们得出结论，与2次试验的T迷宫和恐惧条件任务相比，跨越多天的巴恩斯迷宫任务更适合研究9个月大的APPswe/PS1dE9小鼠中的细微学习和记忆缺陷。该测试显示，与野生型同窝小鼠相比，APPswe/PS1dE9小鼠在空间记忆和认知灵活性方面均存在缺陷。此外，我们得出结论，在这个年龄的这种AD小鼠模型中不存在性别依赖性记忆缺陷差异。
