褪黑激素、褪黑激素受体与睡眠:超越传统观点

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Stefano Comai, Gabriella Gobbi
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引用次数: 0

摘要

睡眠约占人类寿命的三分之一,是身心健康必不可少的重要生理过程。正常的睡眠由清醒、非快速眼动(NREM)睡眠和快速眼动(REM)睡眠有序地进行,所有这些睡眠过程都受到严格的调节。褪黑激素通常被称为 "睡眠激素",它在睡眠/觉醒周期的调节中起着关键作用,并通过称为 MT1 和 MT2 的高亲和性 G 蛋白偶联受体发挥其作用。对这些受体的选择性调节是治疗睡眠障碍的一条很有前景的途径。这篇综述探讨了褪黑素在睡眠调节中的多方面作用,重点是针对MT1和MT2受体的选择性配体,以及涉及MT1和MT2基因敲除小鼠的研究。与一般观点相反,越来越多的证据表明,褪黑激素通过MT1和MT2受体不仅可能影响睡眠的昼夜节律,还可能调节睡眠的平衡过程和睡眠结构,或者说,褪黑激素可能是连接睡眠的平衡调节和昼夜节律调节的分子。此外,还讨论了 MT1 和 MT2 受体在大脑中的不同定位,MT1 受体主要调节快速眼动睡眠,而 MT2 受体则调节非快速眼动睡眠。总之,睡眠调控不仅仅局限于褪黑激素的循环水平和昼夜节律峰值;它还关键地涉及 MT1 和 MT2 受体在参与睡眠调控的各个脑区和核团中的表达、分子激活和调控功能。这项研究强调了持续调查 MT1 和 MT2 受体在睡眠中的选择性作用的重要性。这些研究工作有望为开发有针对性的MT1或MT2受体配体铺平道路,从而优化对睡眠障碍的治疗干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Melatonin, Melatonin Receptors and Sleep: Moving Beyond Traditional Views

Sleep, constituting approximately one-third of the human lifespan, is a crucial physiological process essential for physical and mental well-being. Normal sleep consists of an orderly progression through wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referred to as the “hormone of sleep,” plays a pivotal role as a regulator of the sleep/wake cycle and exerts its effects through high-affinity G-protein coupled receptors known as MT1 and MT2. Selective modulation of these receptors presents a promising therapeutic avenue for sleep disorders. This review examines research on the multifaceted role of melatonin in sleep regulation, focusing on selective ligands targeting MT1 and MT2 receptors, as well as studies involving MT1 and MT2 knockout mice. Contrary to common beliefs, growing evidence suggests that melatonin, through MT1 and MT2 receptors, might not only influence circadian aspects of sleep but likely, also modulate the homeostatic process of sleep and sleep architecture, or could be the molecule linking the homeostatic and circadian regulation of sleep. Furthermore, the distinct brain localization of MT1 and MT2 receptors, with MT1 receptors primarily regulating REM sleep and MT2 receptors regulating NREM sleep, is discussed. Collectively, sleep regulation extends beyond the circulating levels and circadian peak of melatonin; it also critically involves the expression, molecular activation, and regulatory functions of MT1 and MT2 receptors across various brain regions and nuclei involved in the regulation of sleep. This research underscores the importance of ongoing investigation into the selective roles of MT1 and MT2 receptors in sleep. Such research efforts are expected to pave the way for the development of targeted MT1 or MT2 receptors ligands, thereby optimizing therapeutic interventions for sleep disorders.

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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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