Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Center for Basic and Translational Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Nat Commun. 2020 Sep 2;11(1):4411. doi: 10.1038/s41467-020-18115-2.
The glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid transport system is supported by the water channel aquaporin-4 (AQP4) localized to vascular endfeet of astrocytes. The glymphatic system is more effective during sleep, but whether sleep timing promotes glymphatic function remains unknown. We here show glymphatic influx and clearance exhibit endogenous, circadian rhythms peaking during the mid-rest phase of mice. Drainage of CSF from the cisterna magna to the lymph nodes exhibits daily variation opposite to glymphatic influx, suggesting distribution of CSF throughout the animal depends on time-of-day. The perivascular polarization of AQP4 is highest during the rest phase and loss of AQP4 eliminates the day-night difference in both glymphatic influx and drainage to the lymph nodes. We conclude that CSF distribution is under circadian control and that AQP4 supports this rhythm.
水通道蛋白 4（AQP4）定位于星形胶质细胞血管终足，糖酵解系统是一个促进脑脊髓液（CSF）流入大脑并清除代谢废物的血管周围空间网络。该液体转运系统得到水通道蛋白 4（AQP4）的支持。糖酵解系统在睡眠期间更有效，但睡眠时间是否促进糖酵解功能尚不清楚。我们在这里显示糖酵解内流和清除表现出内源性的、节律性的峰值，在小鼠的中休息阶段达到峰值。从脑池到淋巴结的 CSF 引流表现出与糖酵解内流相反的每日变化，这表明 CSF 在整个动物体内的分布取决于一天中的时间。AQP4 的血管周围极化在休息阶段最高，而 AQP4 的缺失消除了糖酵解内流和向淋巴结引流的昼夜差异。我们得出结论，CSF 的分布受昼夜节律控制，AQP4 支持这种节律。
