KI-Alzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum, 5th Floor, SE 14186, Stockholm, Sweden.
Behav Brain Res. 2010 Dec 20;215(1):83-94. doi: 10.1016/j.bbr.2010.06.034. Epub 2010 Jul 6.
Transgenic animals expressing mutant human amyloid precursor protein (APP) are used as models for Alzheimer disease (AD). Ideally, behavioral tests improve the predictive validity of studies on animals by mirroring the functional impact of AD-like neuropathology. Learning and memory studies in APP transgenic models have been difficult to replicate. Standardization of procedures, automatization or improved protocol design can improve reproducibility. Here the IntelliCage, an automated system, was used for behavioral testing of APP female transgenic mice with both the Arctic and Swedish mutations, the tg-ArcSwe model. Protocols covering exploration, operant learning, place learning and extinction of place preference as well as passive avoidance tests were used for longitudinal characterization of behavior. Differences in exploratory activity were significant at four months of age, when plaque-free tg-ArcSwe mice visited less frequently the IntelliCage corners and initially performed fewer visits with licks compared to non-tg animals, inside the new environment. Fourteen months old tg-ArcSwe mice required a longer time to re-habituate to the IntelliCages than non-tg mice. At both ages tg-ArcSwe mice perseverated in place preference extinction test. Fourteen months old tg-ArcSwe mice were impaired in hippocampus-dependent spatial passive avoidance learning. This deficit was found to inversely correlate to calbindin-D28k immunoreactivity in the polymorphic layer of the dentate gyrus. Reduced water intake and body weight were observed in 4 months old tg-ArcSwe animals. The body weight difference increased with age. Thus behavioral and metabolic changes in the tg-ArcSwe APP model were detected using the IntelliCage, a system which provides the opportunity for standardized automated longitudinal behavioral phenotyping.
表达突变人淀粉样前体蛋白（APP）的转基因动物被用作阿尔茨海默病（AD）的模型。理想情况下，行为测试通过模拟 AD 样神经病理学的功能影响来提高动物研究的预测有效性。APP 转基因模型中的学习和记忆研究一直难以复制。程序的标准化、自动化或改进的方案设计可以提高可重复性。在这里，使用自动化系统 IntelliCage 对具有北极和瑞典突变的 APP 雌性转基因小鼠（tg-ArcSwe 模型）进行行为测试。涵盖探索、操作性学习、位置学习和位置偏好消退以及被动回避测试的方案用于纵向行为特征描述。在四个月大时，斑块无的 tg-ArcSwe 小鼠访问 IntelliCage 角落的频率较低，与非转基因动物相比，在新环境中最初舔舐的次数较少，探索性活动的差异具有显著性。14 个月大的 tg-ArcSwe 小鼠重新适应 IntelliCage 的时间比非转基因小鼠长。在两个年龄段，tg-ArcSwe 小鼠在位置偏好消退测试中持续存在。14 个月大的 tg-ArcSwe 小鼠在海马依赖性空间性被动回避学习中受损。发现这种缺陷与多形层中钙结合蛋白-D28k 的免疫反应性呈负相关。在 4 个月大的 tg-ArcSwe 动物中观察到饮水量和体重减少。体重差异随着年龄的增长而增加。因此，使用 IntelliCage 检测到 tg-ArcSwe APP 模型中的行为和代谢变化，该系统为标准化自动化纵向行为表型提供了机会。
