Project Grant R41AG082600

NONINVASIVE SLEEP ENHANCEMENT AND BEHAVIOR MONITORING TECHNOLOGIES FOR ALZHEIMER'S MODEL MICE - 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.