Bmal1 function in skeletal muscle regulates sleep

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...

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Main Authors: J Christopher Ehlen, Allison J Brager, Julie Baggs, Lennisha Pinckney, Cloe L Gray, Jason P DeBruyne, Karyn A Esser, Joseph S Takahashi, Ketema N Paul
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-07-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/26557
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author J Christopher Ehlen
Allison J Brager
Julie Baggs
Lennisha Pinckney
Cloe L Gray
Jason P DeBruyne
Karyn A Esser
Joseph S Takahashi
Ketema N Paul
author_facet J Christopher Ehlen
Allison J Brager
Julie Baggs
Lennisha Pinckney
Cloe L Gray
Jason P DeBruyne
Karyn A Esser
Joseph S Takahashi
Ketema N Paul
author_sort J Christopher Ehlen
collection DOAJ
description 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.
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spelling doaj.art-365d06806a9547f992f58e02edefe6372022-12-22T03:24:42ZengeLife Sciences Publications LtdeLife2050-084X2017-07-01610.7554/eLife.26557Bmal1 function in skeletal muscle regulates sleepJ Christopher Ehlen0https://orcid.org/0000-0003-3223-9262Allison J Brager1Julie Baggs2Lennisha Pinckney3Cloe L Gray4Jason P DeBruyne5Karyn A Esser6https://orcid.org/0000-0002-5791-1441Joseph S Takahashi7https://orcid.org/0000-0003-0384-8878Ketema N Paul8https://orcid.org/0000-0003-0226-9559Neuroscience Institute, Morehouse School of Medicine, Atlanta, United StatesNeuroscience Institute, Morehouse School of Medicine, Atlanta, United States; Behavioral Biology Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, United StatesNeuroscience Institute, Morehouse School of Medicine, Atlanta, United StatesNeuroscience Institute, Morehouse School of Medicine, Atlanta, United StatesNeuroscience Institute, Morehouse School of Medicine, Atlanta, United StatesNeuroscience Institute, Morehouse School of Medicine, Atlanta, United StatesMyology Institute, College of Medicine, University of Florida, Gainesville, United StatesDepartment of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United StatesNeuroscience Institute, Morehouse School of Medicine, Atlanta, United States; Department of Integrative Biology and Physiology, University of California, Los Angeles, California, United StatesSleep 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.https://elifesciences.org/articles/26557bmal1sleepskeletal musclehomeostasisarntl
spellingShingle J Christopher Ehlen
Allison J Brager
Julie Baggs
Lennisha Pinckney
Cloe L Gray
Jason P DeBruyne
Karyn A Esser
Joseph S Takahashi
Ketema N Paul
Bmal1 function in skeletal muscle regulates sleep
eLife
bmal1
sleep
skeletal muscle
homeostasis
arntl
title Bmal1 function in skeletal muscle regulates sleep
title_full Bmal1 function in skeletal muscle regulates sleep
title_fullStr Bmal1 function in skeletal muscle regulates sleep
title_full_unstemmed Bmal1 function in skeletal muscle regulates sleep
title_short Bmal1 function in skeletal muscle regulates sleep
title_sort bmal1 function in skeletal muscle regulates sleep
topic bmal1
sleep
skeletal muscle
homeostasis
arntl
url https://elifesciences.org/articles/26557
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