Sheehan Patrick W, Musiek Erik S
Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States.
Knight Alzheimer's Disease Research Center, Washington University School of Medicine in St. Louis, St. Louis, MO, United States.
Front Neurosci. 2020 Jul 7;14:703. doi: 10.3389/fnins.2020.00703. eCollection 2020.
Circadian dysfunction has been described in patients with symptomatic Alzheimer's disease (AD), as well as in presymptomatic phases of the disease. Modeling this circadian dysfunction in mouse models would provide an optimal platform for understanding mechanisms and developing therapies. While numerous studies have examined behavioral circadian function, and in some cases clock gene oscillation, in mouse models of AD, the results are variable and inconsistent across models, ages, and conditions. Ultimately, circadian changes observed in APP/PS1 models are inconsistent across studies and do not always replicate circadian phenotypes observed in human AD. Other models, including the 3xTG mouse, tau transgenic lines, and the accelerated aging SAMP8 line, show circadian phenotypes more consistent with human AD, although the literature is either inconsistent or minimal. We summarize these data and provide some recommendations to improve and standardize future studies of circadian function in AD mouse models.
昼夜节律功能障碍已在有症状的阿尔茨海默病（AD）患者以及该疾病的症状前阶段中被描述。在小鼠模型中模拟这种昼夜节律功能障碍将为理解机制和开发治疗方法提供一个最佳平台。虽然许多研究已经在AD小鼠模型中研究了行为昼夜节律功能，并且在某些情况下研究了时钟基因振荡，但结果在不同模型、年龄和条件下是可变且不一致的。最终，在APP/PS1模型中观察到的昼夜节律变化在不同研究中并不一致，并且并不总是能复制在人类AD中观察到的昼夜节律表型。其他模型，包括3xTG小鼠、tau转基因系和加速衰老的SAMP8系，显示出与人类AD更一致的昼夜节律表型，尽管文献要么不一致要么很少。我们总结了这些数据，并提供了一些建议，以改进和规范未来AD小鼠模型中昼夜节律功能的研究。
