Kim Pureum, Garner Nicholas, Tatkovic Annaleis, Parsons Rex, Chunduri Prasad, Vukovic Jana, Piper Michael, Pfeffer Martina, Weiergräber Marco, Oster Henrik, Rawashdeh Oliver
School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD Australia.
Present Address: Australian Centres for Health Services Innovation and Healthcare Transformation, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD Australia.
NPJ Biol Timing Sleep. 2024;1(1):13. doi: 10.1038/s44323-024-00013-1. Epub 2024 Nov 1.
Melatonin supplementation strengthens non-restorative sleep rhythms and its temporal alignment in both humans and night-active rodents. Of note, although the sleep cycle is reversed in day-active and night-active (nocturnal) mammals, both, produce melatonin at night under the control of the circadian clock. The effects of exogenous melatonin on sleep and sleepiness are relatively clear, but its endogenous role in sleep, particularly, in timing sleep onset (SO), remains poorly understood. We show in nocturnal mice that the increases in mid-nighttime sleep episodes, and the mid-nighttime decline in activity, are coupled to nighttime melatonin signaling. Furthermore, we show that endogenous melatonin modulates SO by reducing the threshold for wake-to-sleep transitioning. Such link between melatonin and SO timing may explain phenomena such as increased sleep propensity in circadian rhythm sleep disorders and chronic insomnia in patients with severely reduced nocturnal melatonin levels. Our findings demonstrate that melatonin's role in sleep is evolutionarily conserved, effectively challenging the argument that melatonin cannot play a major role in sleep regulation in nocturnal mammals, where the main activity phase coincides with high melatonin levels.
补充褪黑素可加强非恢复性睡眠节律及其在人类和夜间活动啮齿动物中的时间同步性。值得注意的是，尽管昼夜活动和夜间活动（夜行性）哺乳动物的睡眠周期相反，但两者在生物钟的控制下均在夜间分泌褪黑素。外源性褪黑素对睡眠和嗜睡的影响相对明确，但其在睡眠中的内源性作用，尤其是在调节睡眠起始时间（SO）方面，仍知之甚少。我们在夜行性小鼠中发现，午夜睡眠时段的增加以及午夜活动量的下降与夜间褪黑素信号传导相关。此外，我们还表明内源性褪黑素通过降低从觉醒到睡眠转换的阈值来调节睡眠起始时间。褪黑素与睡眠起始时间之间的这种联系可能解释了诸如昼夜节律性睡眠障碍中睡眠倾向增加以及夜间褪黑素水平严重降低患者的慢性失眠等现象。我们的研究结果表明，褪黑素在睡眠中的作用在进化上是保守的，有效地挑战了褪黑素在夜行性哺乳动物睡眠调节中不能发挥主要作用的观点，因为夜行性哺乳动物的主要活动阶段与高褪黑素水平相吻合。
