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Circadian control of brain glymphatic and lymphatic fluid flow

Author

Listed:
  • 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
    Center for Basic and Translational Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen)

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.

Suggested Citation

  • Lauren M. Hablitz & Virginia Plá & Michael Giannetto & Hanna S. Vinitsky & Frederik Filip Stæger & Tanner Metcalfe & Rebecca Nguyen & Abdellatif Benrais & Maiken Nedergaard, 2020. "Circadian control of brain glymphatic and lymphatic fluid flow," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18115-2
    DOI: 10.1038/s41467-020-18115-2
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    Cited by:

    1. Qian Sun & Sisi Peng & Qiwu Xu & Pia Weikop & Rashad Hussain & Wei Song & Maiken Nedergaard & Fengfei Ding, 2024. "Enhancing glymphatic fluid transport by pan-adrenergic inhibition suppresses epileptogenesis in male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Susana Lozano-Tovar & Yaneth Rodríguez-Agudelo & David José Dávila-Ortiz de Montellano & Blanca Estela Pérez-Aldana & Alberto Ortega-Vázquez & Nancy Monroy-Jaramillo, 2023. "Relationship between APOE , PER2 , PER3 and OX2R Genetic Variants and Neuropsychiatric Symptoms in Patients with Alzheimer’s Disease," IJERPH, MDPI, vol. 20(5), pages 1-14, March.
    3. Ryann M. Fame & Peter N. Kalugin & Boryana Petrova & Huixin Xu & Paul A. Soden & Frederick B. Shipley & Neil Dani & Bradford Grant & Aja Pragana & Joshua P. Head & Suhasini Gupta & Morgan L. Shannon &, 2023. "Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Per Kristian Eide & Aslan Lashkarivand & Are Pripp & Lars Magnus Valnes & Markus Herberg Hovd & Geir Ringstad & Kaj Blennow & Henrik Zetterberg, 2023. "Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Chou, Dean & Chen, Po-Yen, 2024. "A machine learning method to explore the glymphatic system via poroelastodynamics," Chaos, Solitons & Fractals, Elsevier, vol. 178(C).

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