阿尔茨海默病小鼠模型的行为学检测:实用考虑因素与指南。
Behavioral assays with mouse models of Alzheimer's disease: practical considerations and guidelines.
机构信息
Department of Bio-Medical Sciences - Section of Physiology, University of Catania, Viale A. Doria 6, Catania 95125, Italy.
Department of Pathology & Cell Biology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, P&S #12-420D, 630W 168th Street, New York, NY 10032, USA.
出版信息
Biochem Pharmacol. 2014 Apr 15;88(4):450-67. doi: 10.1016/j.bcp.2014.01.011. Epub 2014 Jan 21.
In Alzheimer's disease (AD) basic research and drug discovery, mouse models are essential resources for uncovering biological mechanisms, validating molecular targets and screening potential compounds. Both transgenic and non-genetically modified mouse models enable access to different types of AD-like pathology in vivo. Although there is a wealth of genetic and biochemical studies on proposed AD pathogenic pathways, as a disease that centrally features cognitive failure, the ultimate readout for any interventions should be measures of learning and memory. This is particularly important given the lack of knowledge on disease etiology - assessment by cognitive assays offers the advantage of targeting relevant memory systems without requiring assumptions about pathogenesis. A multitude of behavioral assays are available for assessing cognitive functioning in mouse models, including ones specific for hippocampal-dependent learning and memory. Here we review the basics of available transgenic and non-transgenic AD mouse models and detail three well-established behavioral tasks commonly used for testing hippocampal-dependent cognition in mice - contextual fear conditioning, radial arm water maze and Morris water maze. In particular, we discuss the practical considerations, requirements and caveats of these behavioral testing paradigms.
在阿尔茨海默病(AD)的基础研究和药物发现中,小鼠模型是揭示生物学机制、验证分子靶点和筛选潜在化合物的重要资源。转基因和非基因修饰的小鼠模型都可以在体内模拟不同类型的 AD 样病理学。尽管在 AD 发病机制的提议途径上已经有大量的遗传和生化研究,但作为一种以认知失败为中心的疾病,任何干预措施的最终结果都应该是学习和记忆的衡量标准。鉴于对疾病病因的了解不足,这一点尤其重要——认知测试的评估具有靶向相关记忆系统的优势,而无需对发病机制做出假设。有多种行为测试可用于评估小鼠模型的认知功能,包括特定于海马依赖性学习和记忆的测试。在这里,我们回顾了现有的转基因和非转基因 AD 小鼠模型的基础知识,并详细介绍了三种常用于测试小鼠海马依赖性认知的成熟行为任务——情境恐惧条件反射、放射臂水迷宫和 Morris 水迷宫。特别是,我们讨论了这些行为测试范式的实际考虑因素、要求和注意事项。