Pévet P
UPR 3212, CNRS-university of Strasbourg, institute for cellular and integrative neurosciences, 5, rue Blaise-Pascal, 67084 Strasbourg, France.
Rev Neurol (Paris). 2014 Nov;170(11):646-52. doi: 10.1016/j.neurol.2014.05.008. Epub 2014 Oct 5.
Daily rhythms in physiological and behavioural processes are controlled by a network of circadian clocks. In mammals, at the top of the network is a master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the SCN clock. Several roles of melatonin in the circadian system have been identified. As a major hormonal output, melatonin distributes temporal cues generated by the SCN to the multitude of tissues expressing melatonin receptors. In some target tissues, these melatonin signals can drive daily rhythmicity that would otherwise be lacking. In other target structures, melatonin signals are used for the synchronization (i.e., adjustment of the timing of existing oscillations) of peripheral oscillators. Due to the expression of melatonin receptors in the SCN, endogenous melatonin is also able to feedback onto the master clock. Of note, pharmacological treatment with exogenous melatonin can synchronize the SCN clock. From a clinical point of view, provided that the subject is not exposed to light at night, the daily profile of circulating melatonin provides a reliable estimate of the timing of the human SCN. During the past decade, a number of melatonin agonists have been developed. These drugs may target the SCN for improving circadian timing or act indirectly at some downstream level of the circadian network to restore proper internal synchronization.
生理和行为过程中的日常节律由昼夜节律时钟网络控制。在哺乳动物中，该网络的顶端是位于下丘脑视交叉上核（SCN）的主时钟。松果体夜间褪黑素的合成和释放受SCN时钟严格控制。褪黑素在昼夜节律系统中的多种作用已被确定。作为主要的激素输出，褪黑素将SCN产生的时间线索传递给众多表达褪黑素受体的组织。在一些靶组织中，这些褪黑素信号可驱动原本缺乏的日常节律性。在其他靶结构中，褪黑素信号用于外周振荡器的同步（即调整现有振荡的时间）。由于SCN中存在褪黑素受体表达，内源性褪黑素也能够反馈到主时钟上。值得注意的是，外源性褪黑素的药物治疗可使SCN时钟同步。从临床角度来看，只要受试者夜间不暴露于光线下，循环褪黑素的每日变化情况就能可靠地估计人类SCN的时间。在过去十年中，已开发出多种褪黑素激动剂。这些药物可能靶向SCN以改善昼夜节律时间，或在昼夜节律网络的某些下游水平间接起作用以恢复适当的内部同步。
