Bmal1 function in skeletal muscle regulates sleep
Bmal1 function in skeletal muscle regulates sleep
复制标题
DOI：
10.7554/elife.26557
复制
发表时间：
2017-07-20
期刊：
影响因子：
7.7
通讯作者：
Paul, Ketema N.
中科院分区：
文献类型：
--
作者：
Ehlen, J. Christopher;Brager, Allison J.;Paul, Ketema N.
睡眠不足会严重损害人的工作能力，但人们对从睡眠不足中恢复过来的能力还不太了解。由于睡眠的强烈行为表现，睡眠调节过程被认为只存在于大脑中。小鼠体内生物钟基因Bmal1的全身敲除会影响睡眠的几个方面，然而，负责的细胞/组织尚不清楚。我们发现，恢复Bmal1基因敲除小鼠大脑中的Bmal1表达并不能挽救Bmal1依赖的睡眠表型。令人惊讶的是，大多数睡眠量表型，而不是睡眠时间表型，可以分别通过敲除或恢复骨骼肌中的BMAL1来复制或挽救。我们还发现，骨骼肌Bmal1的过度表达会降低睡眠不足后的恢复反应。总之，这些发现表明骨骼肌中的Bmal1表达是调节总睡眠量的必要和充分条件，并揭示了正常睡眠调节的关键成分发生在肌肉中。
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.