0216 Behavioral State Recording & Sleep Deprivation in Mice to Explore the Underlying Mechanisms of Alzheimer’s Disease

Abstract Introduction Alzheimer's disease (AD), the most common form of dementia in the US, affecting 6.5 million individuals with a total healthcare cost of $321 billion, is characterized by cognitive dysfunction, memory problems, and disrupted sleep. Mice are crucial for studying AD and sleep patterns in humans, but current methods for inducing sleep disruption have limitations such as wired telemetry, real-time monitoring challenges, and disrupting the mouse's home environment. Better tools are needed to maximize the potential of mouse models in AD and sleep research. Objectives: This study aims to fill this gap by developing a novel system of sleep deprivation in mice to explore the underlying mechanisms connecting sleep and AD. Methods This study utilized a combination of DSI Co. wireless telemetry, Spike-2 software from CED Co., and third-party olfactory controllers to achieve automatic sleep deprivation via air-puffs. C57BL/6J (B6) mice were utilized for validation of the behavioral state recording/sleep deprivation system and preliminary biological analyses. The system was employed to achieve sleep deprivation in mice for 9 hours, then blood and brain tissue were collected for subsequent genetic analysis. qPCR was then applied to determine the expression of genes of interest related to AD, which was utilized in combination with analysis of variance to elucidate significance. Results Behavioral state recordings indicate the system can accurately collect and analyze telemetry signals in real time then initiate an air-puff, which successfully wakes the animal. qPCR results indicate a significant decrease in DNA damage repair enzyme and an increase in inflammatory cytokine gene expression, relative to controls, following ~9 hours of sleep deprivation (p< 0.05). These results collectively indicate the progression of an AD-phenotype. Conclusion These preliminary results indicate this novel system of behavioral state recording and sleep deprivation in mice can be applied to successfully explore the underlying mechanisms connecting sleep and AD. Future studies will extend to further proteomic and epigenetic analyses and explore specific sleep stages in relation to AD-progression. Support (if any) Center for Therapeutic Innovation (CTI