Circadian control of brain glymphatic and lymphatic fluid flow

Lauren M. Hablitz (), Virginia Plá, Michael Giannetto, Hanna S. Vinitsky, Frederik Filip Stæger, Tanner Metcalfe, Rebecca Nguyen, Abdellatif Benrais and Maiken Nedergaard ()
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Lauren M. Hablitz: Center for Translational Neuromedicine, University of Rochester Medical Center
Virginia Plá: Center for Translational Neuromedicine, University of Rochester Medical Center
Michael Giannetto: Center for Translational Neuromedicine, University of Rochester Medical Center
Hanna S. Vinitsky: Center for Translational Neuromedicine, University of Rochester Medical Center
Frederik Filip Stæger: Center for Basic and Translational Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen
Tanner Metcalfe: Center for Translational Neuromedicine, University of Rochester Medical Center
Rebecca Nguyen: Center for Translational Neuromedicine, University of Rochester Medical Center
Abdellatif Benrais: Center for Translational Neuromedicine, University of Rochester Medical Center
Maiken Nedergaard: Center for Translational Neuromedicine, University of Rochester Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-18115-2

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