Circadian control of brain glymphatic and lymphatic fluid flow
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 02, 2020
- Source ID
- 10.1038/s41467-020-18115-2
Entities
People
- Abdellatif Benrais
- Frederik Filip Stæger
- Hanna S Vinitsky
- Lauren M Hablitz
- Maiken Nedergaard
- Michael Giannetto
- Rebecca Nguyen
- Tanner Metcalfe
- Virginia Plá
Organizations
- Army Research Office
- National Institute of Neurological Disorders and Stroke
- United States Department of Health and Human Services