1. Neuroscience
Download icon

Bmal1 function in skeletal muscle regulates sleep

  1. J Christopher Ehlen
  2. Allison J Brager
  3. Julie Baggs
  4. Lennisha Pinckney
  5. Cloe L Gray
  6. Jason P DeBruyne
  7. Karyn A Esser
  8. Joseph S Takahashi
  9. Ketema N Paul Is a corresponding author
  1. Morehouse School of Medicine, United States
  2. University of Florida, United States
  3. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States
Short Report
Cited
0
Views
2,834
Comments
0
Cite as: eLife 2017;6:e26557 doi: 10.7554/eLife.26557

Abstract

Sleep loss can severely impair the ability to perform, yet the ability to recover from sleep loss is not well understood. Sleep regulatory processes are assumed to lie exclusively within the brain mainly due to the strong behavioral manifestations of sleep. Whole-body knockout of the circadian clock gene Bmal1 in mice affects several aspects of sleep, however, the cells/tissues responsible are unknown. We found that restoring Bmal1 expression in the brains of Bmal1-knockout mice did not rescue Bmal1-dependent sleep phenotypes. Surprisingly, most sleep-amount, but not sleep-timing, phenotypes could be reproduced or rescued by knocking out or restoring BMAL1 exclusively in skeletal muscle, respectively. We also found that overexpression of skeletal-muscle Bmal1 reduced the recovery response to sleep loss. Together, these findings demonstrate that Bmal1 expression in skeletal muscle is both necessary and sufficient to regulate total sleep amount and reveal that critical components of normal sleep regulation occur in muscle.

Article and author information

Author details

  1. J Christopher Ehlen

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    No competing interests declared.
    ORCID icon 0000-0003-3223-9262
  2. Allison J Brager

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    No competing interests declared.
  3. Julie Baggs

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    No competing interests declared.
  4. Lennisha Pinckney

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    No competing interests declared.
  5. Cloe L Gray

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    No competing interests declared.
  6. Jason P DeBruyne

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    Competing interests
    No competing interests declared.
  7. Karyn A Esser

    Myology Institute, College of Medicine, University of Florida, Gainsville, United States
    Competing interests
    No competing interests declared.
    ORCID icon 0000-0002-5791-1441
  8. Joseph S Takahashi

    Department of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    Joseph S Takahashi, Reviewing editor, eLife.
    ORCID icon 0000-0003-0384-8878
  9. Ketema N Paul

    Neuroscience Institute, Morehouse School of Medicine, Atlanta, United States
    For correspondence
    ketema.paul@ucla.edu
    Competing interests
    No competing interests declared.
    ORCID icon 0000-0003-0226-9559

Funding

National Institute on Minority Health and Health Disparities (G12 MD007602)

  • J Christopher Ehlen
  • Jason P DeBruyne

National Institute of Neurological Disorders and Stroke (R01 NS078410)

  • Ketema N Paul

National Heart, Lung, and Blood Institute (T32 HL116077)

  • Allison J Brager

National Institute of Mental Health (P50 MH074924)

  • Joseph S Takahashi

National Institute of General Medical Sciences (SC1 GM109861)

  • Jason P DeBruyne

Howard Hughes Medical Institute

  • Joseph S Takahashi

National Heart, Lung, and Blood Institute (T32 HL007609)

  • Cloe L Gray

National Institute of Neurological Disorders and Stroke (U54 NS060659)

  • Ketema N Paul

National Institute of Neurological Disorders and Stroke (U54 NS083932)

  • J Christopher Ehlen
  • Jason P DeBruyne
  • Ketema N Paul

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense.

Ethics

Animal experimentation: All procedures involving animals were approved by the Morehouse School of Medicine institutional animal care and use committee, protocol reference number 15-17. Animal studies conformed to recommendations published in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

Reviewing Editor

  1. Louis J Ptáček, Reviewing Editor, University of California, San Francisco, United States

Publication history

  1. Received: March 6, 2017
  2. Accepted: July 12, 2017
  3. Accepted Manuscript published: July 20, 2017 (version 1)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,834
    Page views
  • 660
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Scopus, Crossref.

Comments

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)