Noninvasive sleep enhancement and behavior monitoring technologies for Alzheimer's model mice

该项目的目标是开发新技术来识别和跟踪睡眠和觉醒 阿尔茨海默病（AD）小鼠模型中存在的异常，以及测试睡眠增强 用于AD动物研究的技术。Signal Solutions，LLC此前已开发并 商业化了一种基于压电的系统，用于无创、高通量的睡眠和唤醒监测， 啮齿动物睡眠和清醒的自动评分允许在更长时间内同时记录许多动物 周期，对研究人员的负担很小，可与更复杂， 昂贵的表演。 睡眠和清醒时的行为变化可能先于阿尔茨海默氏症进展中的记忆丧失 疾病（AD）。临床研究表明，睡眠障碍在AD患者中的比例很高。 AD的动物模型也显示睡眠障碍，并且一些模型显示觉醒行为的变化 在分子标志和记忆问题出现之前，就像在人类AD中明显发生的那样。治疗 对于AD，一个潜在的治疗靶点是防止致病形式的淀粉样蛋白-β（A-β）聚集 和tau。大脑中的废物清除已被证明随着睡眠的增加而增加，包括 A β的清除率。最近，使用用于摇动的机械装置的非药理学方法已经 显示出增强睡眠的前景，这可以应用于AD研究。 该项目的具体目标是：1）开发先进的睡眠/觉醒跟踪技术： 新的多点触摸传感器，我们目前的压电技术，一起将识别特定的行为 与AD进展相关，用AD小鼠模型3xTg测试。2)改善睡眠 技术：修改我们目前的MouseQwake睡眠中断系统，以实现机械睡眠增强， 具有睡眠和唤醒跟踪功能。 预期成果：设想的产品是一个家庭笼传感器和软件，将允许 研究人员可以准确测量长期AD疾病进展期间睡眠和觉醒的变化， 并跟踪AD模型小鼠行为的细微变化。这个系统将减少工作量，时间 测试行为，以及分析视频或电生理学的时间，这是目前的主要瓶颈。 一个扩展的MouseQwake系统将提供一个睡眠操纵的工具， 中断以及同时的睡眠/觉醒和行为记录。如果成功，第二阶段调查 将涉及多个AD啮齿动物模型的大规模研究，并继续对两者进行迭代改进 第一阶段开发的硬件和软件。

The aims of this project are to develop new technologies to identify and track sleep and wake abnormalities present in mouse models of Alzheimer’s disease (AD), as well as to test a sleep enhancement technology for applications in AD animal research. Signal Solutions, LLC, has previously developed and commercialized a piezoelectric based system for noninvasive, high-throughput sleep and wake monitoring of rodents. Automated scoring of sleep and wake allows for simultaneous recordings of many animals over longer periods, with little burden on the researcher, rivalling EEG/EMG methods that are more complicated and expensive to perform. Behavioral changes in sleep and wake can precede memory loss in the progression of Alzheimer’s disease (AD). Clinical studies suggest sleep disturbances are exhibited in a high percentage of AD patients. Animal models of AD also display sleep disturbances and some models show changes in wake behaviors before the molecular hallmarks and memory problems appear, as clearly occurs in human AD. In the treatment of AD, a potential therapeutic target is preventing the aggregation of pathogenic forms of amyloid-beta (A-beta) and tau. Waste clearance in the brain has been shown to be increased with increased sleep, including clearance of A-beta. Recently, non-pharmacological approaches using mechanical devices for rocking have shown promise for sleep enhancement, which could be applied to AD research. The specific aims of this project are to 1) Develop advanced sleep/wake tracking technology: Add a new multipoint touch sensor to our current piezoelectric technology that together will identify specific behaviors associated with AD progression, tested with AD mouse model 3xTg. 2) Develop Sleep Enhancement Technology: Modify our current MouseQwake sleep-disruption system for mechanical sleep-enhancement, with companion sleep and wake tracking capabilities. Anticipated Outcomes: The envisioned product is a home cage sensor and software that will allow researchers to accurately measure changes in sleep and wake during long-term AD disease progression, as well as track subtle changes in behavior in AD model mice. This system will minimize the amount of work, time testing behaviors, and time for analyzing the videos or electrophysiology that is currently a major bottleneck. An expanded MouseQwake system will provide a tool for sleep manipulation of both sleep enhancement and disruption as well as simultaneous sleep/wake and behavioral recording. If successful, a Phase II investigation will involve large scale studies of multiple AD rodent models, and continue iterative improvements to both hardware and software developed in phase I.