Bmal1 function in skeletal muscle regulates sleep

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.DOI: http://dx.doi.org/10.7554/eLife.26557.001

Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice

“…Despite its essential role for circadian clock function, BMAL1 has been linked with a number of other non-rhythmic processes such as adipogenesis [45], sleep regulation [16] and cartilage homeostasis [15]. Thus, we asked whether the decreased susceptibility to LPS observed in myBmal-KO mice was due to non-temporal functions of BMAL1 rather than to the disruption of local myeloid clocks.…”

Galanin neurons in the hypothalamus link sleep homeostasis, body temperature and actions of the α2 adrenergic agonist dexmedetomidine

“…Sik3, Adora1, clock, mGluR5, per3, reverba) have been found to modulate sleep homeostasis (9,(11)(12)(13)(14)(15)(16)(17). Astrocytes and skeletal muscle release messengers which can modulate the process (18,19). But in mammals little is known about how sleep homeostasis might work at the neuronal circuit level, or even whether the homeostatic drive is primarily locally or globally determined (20)(21)(22).…”

For everything there is a season: biological rhythms in psychiatry

“…Mice with increased Bmal1 also slept substantially less during the 24 hours after sleep deprivation. 2 'When we first saw the importance of the muscle, we were surprised,' says senior author Ketema Paul, UCLA associate professor of integrative biology and physiology. 'At first we didn't believe it, so we repeated the experiment several times.…”

“…Genetically engineering mice that lack Bmal1 sleep for longer, show increased intensity of non-rapid eye movement sleep and recover from sleep deprivation more slowly than those with Bmal1. 2 Restoring Bmal1 in the brain had no effect on recovery after sleep deficits. Restoring Bmal1 in skeletal muscle, however, enabled mice to rebound from sleep deficits more quickly.…”

“…Indeed, a new study offers the first evidence that a biological clock in skeletal muscle in mice communicates with the brain to influence the most fundamental circadian rhythm -sleep. 2 At the end of a cue… Circadian rhythms allow organisms to synchronise activities and behaviours with patterns of threats and opportunities in the environment, such as food availability, the risk of encountering predators and chances to mate. 1 Indeed, almost every aspect of mammalian physiology shows circadian rhythms, including cardiovascular, nervous, digestive and urinary function.…”