Cross-species translation of the Morris maze for Alzheimer's disease
Cross-species translation of the Morris maze for Alzheimer's disease
复制标题
DOI：
10.1172/jci78464
复制
发表时间：
2016-02-01
影响因子：
15.9
通讯作者：
Finkbeiner, Steven
中科院分区：
文献类型：
--
作者：
Possin, Katherine L.;Sanchez, Pascal E.;Finkbeiner, Steven
需要在动物模型和人类患者之间进行类似的行为分析，以改进翻译研究。在这里，我们检查了在Morris水迷宫中的表现，这是对啮齿动物空间学习和记忆最常用的行为测试，在多大程度上转化为人类。我们为人类受试者设计了一个虚拟版本的测试，其中包括可见目标训练、隐藏目标学习和探测试验，这些试验通常在小鼠版本中进行。我们比较了表达人类淀粉样前体蛋白(HAPP)的转基因小鼠和阿尔茨海默病引起的轻度认知障碍患者(MCI-AD)，以评估绩效指标在检测缺陷方面的敏感性。患者在可见目标训练中表现正常，而Happ小鼠表现出程序性学习缺陷。在隐藏目标学习和探测试验中，Happ小鼠和MCI-AD患者在学习和记忆目标位置方面表现出类似的缺陷。此外，我们还提供了选择绩效指标和样本大小的建议，以使这些检测方法对患有MCI-AD的人类和小鼠模型的学习和记忆缺陷敏感。总之，我们的结果表明，经过仔细的研究设计和分析，Morris迷宫是检测跨物种AD相关损害的敏感方法。
Analogous behavioral assays are needed across animal models and human patients to improve translational research. Here, we examined the extent to which performance in the Morris water maze the most frequently used behavioral assay of spatial learning and memory in rodents translates to humans. We designed a virtual version of the assay for human subjects that includes the visible-target training, hidden-target learning, and probe trials that are typically administered in the mouse version. We compared transgenic mice that express human amyloid precursor protein (hAPP) and patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) to evaluate the sensitivity of performance measures in detecting deficits. Patients performed normally during visible-target training, while hAPP mice showed procedural learning deficits. In hidden-target learning and probe trials, hAPP mice and MCI-AD patients showed similar deficits in learning and remembering the target location. In addition, we have provided recommendations for selecting performance measures and sample sizes to make these assays sensitive to learning and memory deficits in humans with MCI-AD and in mouse models. Together, our results demonstrate that with careful study design and analysis, the Morris maze is a sensitive assay for detecting AD relevant impairments across species.