AANAT1 functions in astrocytes to regulate sleep homeostasis

  1. Sejal Davla
  2. Gregory Artiushin
  3. Yongjun Li
  4. Daryan Chitsaz
  5. Sally Li
  6. Amita Sehgal
  7. Donald J van Meyel  Is a corresponding author
  1. McGill University, Canada
  2. University of Pennsylvania, United States
  3. Howard Hughes Medical Institute, University of Pennsylvania, United States

Abstract

How the brain controls the need and acquisition of recovery sleep after prolonged wakefulness is an important issue in sleep research. The monoamines serotonin and dopamine are key regulators of sleep in mammals and in Drosophila. We found that the enzyme arylalkylamine N-acetyltransferase 1 (AANAT1) is expressed by Drosophila astrocytes and specific subsets of neurons in the adult brain. AANAT1 acetylates monoamines and inactivates them, and we found that AANAT1 limited the accumulation of serotonin and dopamine in the brain upon sleep deprivation. Loss of AANAT1 from astrocytes, but not from neurons, caused flies to increase their daytime recovery sleep following overnight sleep deprivation. Together, these findings demonstrate a crucial role for AANAT1 and astrocytes in the regulation of monoamine bioavailability and homeostatic sleep.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sejal Davla

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
  2. Gregory Artiushin

    Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  3. Yongjun Li

    Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  4. Daryan Chitsaz

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
  5. Sally Li

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
  6. Amita Sehgal

    Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    Amita Sehgal, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7149-8588
  7. Donald J van Meyel

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    For correspondence
    don.vanmeyel@mcgill.ca
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6075-8599

Funding

Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-05142)

  • Donald J van Meyel

Canadian Institutes of Health Research (MOP-137034)

  • Donald J van Meyel

National Institutes of Health (DK120757)

  • Amita Sehgal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Davla et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sejal Davla
  2. Gregory Artiushin
  3. Yongjun Li
  4. Daryan Chitsaz
  5. Sally Li
  6. Amita Sehgal
  7. Donald J van Meyel
(2020)
AANAT1 functions in astrocytes to regulate sleep homeostasis
eLife 9:e53994.
https://doi.org/10.7554/eLife.53994

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https://doi.org/10.7554/eLife.53994