School of Physics, University of Sydney, Sydney, NSW, 2006, Australia.
Center of Excellence for Integrative Brain Function, University of Sydney, Sydney, NSW, 2006, Australia.
Sci Rep. 2022 Aug 12;12(1):13740. doi: 10.1038/s41598-022-15109-6.
Accumulation of waste in cortical tissue and glymphatic waste clearance via extracellular voids partly drives the sleep-wake cycle and modeling has reproduced much of its dynamics. Here, new modeling incorporates higher void volume and clearance in sleep, multiple waste compounds, and clearance obstruction by waste. This model reproduces normal sleep-wake cycles, sleep deprivation effects, and performance decreases under chronic sleep restriction (CSR). Once fitted to calibration data, it successfully predicts dynamics in further experiments on sleep deprivation, intermittent CSR, and recovery after restricted sleep. The results imply a central role for waste products with lifetimes similar to tau protein. Strong tau buildup is predicted if pathologically enhanced production or impaired clearance occur, with runaway buildup above a critical threshold. Predicted tau accumulation has timescales consistent with the development of Alzheimer's disease. The model unifies a wide sweep of phenomena, clarifying the role of glymphatic clearance and targets for interventions against waste buildup.
皮质组织中废物的积累和通过细胞外空隙的神经胶质淋巴系统清除作用部分驱动了睡眠-觉醒周期，模型已经复制了其大部分动力学。在这里，新的模型纳入了更多的睡眠时的空隙体积和清除率、多种废物化合物以及废物清除阻塞。该模型复制了正常的睡眠-觉醒周期、睡眠剥夺效应以及慢性睡眠限制（CSR）下的表现下降。一旦拟合到校准数据，它就成功地预测了睡眠剥夺、间歇性 CSR 以及限制睡眠后的恢复等进一步实验的动态。结果表明，废物产物具有类似于 tau 蛋白的半衰期，在中央起关键作用。如果病理性地增强了产生或受损了清除，则会预测到 tau 出现失控性积累，超过一个临界阈值。预测的 tau 积累的时间尺度与阿尔茨海默病的发展一致。该模型统一了广泛的现象，阐明了神经胶质淋巴系统清除作用的作用以及针对废物积累的干预靶点。
