Alava Bryan R, Morris Andrew R, Liu Andrew C, Abisambra Jose F, Esser Karyn A
Department of Physiology and Aging, University of Florida, Gainesville, FL USA.
Center for Translational Research in Neurodegenerative Disease (CTRND), University of Florida, Gainesville, FL USA.
NPJ Biol Timing Sleep. 2024;1(1):8. doi: 10.1038/s44323-024-00009-x. Epub 2024 Oct 1.
Sleep timing and quantity disturbances persist in tauopathy patients. This has been studied in transgenic models of primary tau neuropathology using traditional electroencephalograms (EEGs) and more recently, the PiezoSleep Mouse Behavioral Tracking System. Here, we generated a primary tauopathy model using an intracerebroventricular injection of human mutant hSyn-P301L-tau, using adeno-associated virus of serotype 8 (AAV8). We discovered distinctions in sleep architecture with altered quantity and timing in AAV8-P301L tau expressing mice of both sexes using the noninvasive PiezoSleep System. The AAV8-P301L tau mice exhibit striking age-related increases in sleep duration specifically at the active phase onset, suggesting a critical and sensitive time-of-day for tauopathy related sleep disturbances to occur. Since our findings show sleep behavior changes at specific transitional periods of the day, tau neuropathology may impact normal diurnal variation in biological processes, which should be explored using the AAV8-P301L tauopathy model.
睡眠时间和数量紊乱在tau蛋白病患者中持续存在。这一点已在原发性tau蛋白神经病理学的转基因模型中进行了研究，使用的是传统脑电图（EEG），最近也使用了PiezoSleep小鼠行为追踪系统。在此，我们通过脑室内注射人突变型hSyn-P301L-tau，利用8型腺相关病毒（AAV8）构建了一种原发性tau蛋白病模型。我们使用非侵入性的PiezoSleep系统发现，在表达AAV8-P301L tau的雌雄小鼠中，睡眠结构存在差异，睡眠数量和时间发生了改变。AAV8-P301L tau小鼠在活跃期开始时睡眠持续时间出现显著的年龄相关增加，这表明tau蛋白病相关睡眠障碍发生的关键且敏感的时间点。由于我们的研究结果显示在一天中的特定过渡时期睡眠行为发生了变化，tau蛋白神经病理学可能会影响生物过程中的正常昼夜变化，这一点应使用AAV8-P301L tau蛋白病模型进行探索。
