Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Neurology, University of Utah, Salt Lake City, UT 84108, USA.
Neuron. 2019 Sep 25;103(6):1044-1055.e7. doi: 10.1016/j.neuron.2019.07.026. Epub 2019 Aug 28.
Sleep is crucial for our survival, and many diseases are linked to long-term poor sleep quality. Before we can use sleep to enhance our health and performance and alleviate diseases associated with poor sleep, a greater understanding of sleep regulation is necessary. We have identified a mutation in the β-adrenergic receptor gene in humans who require fewer hours of sleep than most. In vitro, this mutation leads to decreased protein stability and dampened signaling in response to agonist treatment. In vivo, the mice carrying the same mutation demonstrated short sleep behavior. We found that this receptor is highly expressed in the dorsal pons and that these ADRB1 neurons are active during rapid eye movement (REM) sleep and wakefulness. Activating these neurons can lead to wakefulness, and the activity of these neurons is affected by the mutation. These results highlight the important role of β-adrenergic receptors in sleep/wake regulation.
睡眠对我们的生存至关重要，许多疾病都与长期睡眠质量差有关。在我们能够利用睡眠来增强健康和表现，减轻与睡眠不佳相关的疾病之前，我们需要更好地了解睡眠调节机制。我们在人类中发现了一种β-肾上腺素能受体基因突变，这些人需要的睡眠时间比大多数人少。在体外，这种突变导致蛋白稳定性降低，并对激动剂治疗的信号反应减弱。在体内，携带相同突变的小鼠表现出短睡眠行为。我们发现这种受体在脑桥背侧高度表达，并且这些 ADRB1 神经元在快速眼动（REM）睡眠和觉醒期间活跃。激活这些神经元可以导致觉醒，并且这些神经元的活动受到突变的影响。这些结果强调了β-肾上腺素能受体在睡眠/觉醒调节中的重要作用。
