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

这个项目的目标是开发新的技术来识别和跟踪睡眠和醒来 阿尔茨海默病(AD)小鼠模型中存在的异常以及测试睡眠改善 在AD动物研究中的应用技术。Signal Solutions，LLC之前开发了和 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的时间内同时记录许多动物 周期，在对研究人员几乎没有负担的情况下，可以与更复杂和 表演成本很高。 在阿尔茨海默病的发展过程中，睡眠和清醒的行为变化可以先于记忆丧失 疾病(AD)。临床研究表明，睡眠障碍在很高比例的AD患者中表现出来。 阿尔茨海默病的动物模型也表现出睡眠障碍，一些模型表现出觉醒行为的变化 在分子特征和记忆问题出现之前，就像人类阿尔茨海默病明显发生的那样。在治疗中 阿尔茨海默病的一个潜在治疗靶点是防止致病形式的淀粉样β蛋白(A-β)的聚集 还有陶。大脑中的废物清除已被证明随着睡眠的增加而增加，包括 清除A-β蛋白。最近，使用机械设备进行摇摆的非药理学方法已经 显示了改善睡眠的前景，这可以应用于AD的研究。 该项目的具体目标是：1)开发先进的睡眠/清醒跟踪技术：增加一个 新的多点触摸传感器与我们目前的压电技术相结合，将识别特定的行为 与AD进展相关，用AD模型3xTg进行测试。2)开发睡眠增强功能 技术：将我们目前的鼠标Q唤醒睡眠中断系统改造为机械睡眠增强， 具有同伴睡眠和唤醒跟踪功能。 预期结果：设想的产品是一个家庭笼子传感器和软件，将允许 研究人员准确测量长期AD疾病进展过程中睡眠和清醒的变化，如 以及追踪AD模型小鼠行为的细微变化。该系统将最大限度地减少工作量、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。 扩展的鼠标Q唤醒系统将为睡眠增强和睡眠操作提供一个工具 中断以及同时睡眠/唤醒和行为记录。如果成功，将进行第二阶段调查 将涉及多个AD啮齿动物模型的大规模研究，并继续对这两个模型进行迭代改进 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.