LIGHT-INDUCED SUPPRESSION OF MELATONIN IN ADVANCED AND DELAYED SLEEP

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在过去的几年中，在揭示哺乳动物昼夜节律产生的分子基础方面取得了巨大进展。这些对啮齿动物和苍蝇的分子研究激发了对可能导致人类昼夜节律改变和/或睡眠障碍的遗传差异的研究。人类最常见的两种睡眠障碍被认为是由于昼夜节律的改变而引起的，它们被归类为睡眠阶段延迟综合征（DSPS）和睡眠阶段提前综合征（asp）。DSPS的特征是在凌晨2点至6点之前持续无法入睡，并且在上午10点至下午1点之前难以醒来，而ASPS的特征是习惯性和非自愿的睡眠和醒来时间至少比社会标准早几个小时。最常见的抱怨是在下午晚些时候或晚上犯困，以及凌晨2-5点醒来。基于对大家庭的研究，最近有两份报告表明，ASPS和DSPS都可能有遗传基础，并且可能是由于至少两个新发现的生物钟基因的等位基因差异。此外，最近一项对散发性DSPS的研究表明，第二个时钟基因的等位基因差异可能是这种情况的基础。虽然对DSPS和ASPS的遗传基础的研究代表了一个新的和令人兴奋的途径来阐明睡眠-觉醒和生物钟系统如何相互整合，以及特定生物钟基因的改变如何导致睡眠和觉醒时间的改变，但我们对这些昼夜节律睡眠障碍的生理机制的理解实际上是相当有限的。美国国立卫生研究院资助的母公司的目标之一是测试各种假设，这些假设可以解释昼夜节律系统的改变如何导致睡眠-觉醒周期相对于光-暗周期的阶段变化。该项目的目的是验证这样一种假设，即ASPS或DSPS的昼夜节律阶段改变是由于生物钟对光的反应方式发生了改变。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Over the past few years great progress has been made in uncovering the molecular basis for the generation of circadian rhythms in mammals. These molecular studies in rodents and flies have stimulated a search for genetic differences that could underlie altered circadian rhythms and/or sleep disorders in humans. Two of the most common sleep disorders in humans that are thought to be due to alterations in circadian timing are classified as the Delayed Sleep Phase Syndrome (DSPS) and Advanced Sleep Phase Syndrome (ASPS). DSPS is characterized by a persistent inability to initiate sleep before 2 to 6 AM and difficulty waking up until 10 AM to 1 PM, whereas, ASPS is characterized by habitual and involuntary sleep and wake times that are at least several hours earlier than societal means. The most common complaints are sleepiness in the late afternoon or evening, and early morning awakening of 2-5 AM. Based on studies of extended families, there are now two recent reports indicating that both ASPS and DSPS can have a genetic basis, and may be due to allelic differences in at least two of the newly discovered circadian clock genes. In addition, a recent study of sporadic DSPS indicates that allelic differences in a second clock gene may underlie this condition. While studies on the genetic basis of DSPS and ASPS represent a new and exciting avenue to elucidate how the sleep-wake and circadian clock systems are integrated with each other, and how alterations in specific circadian clock genes can lead to alterations in the timing of sleep and wake, our understanding of the physiological mechanisms responsible for these circadian sleep disorders is actually quite limited. One of the objectives of the parent NIH funded grant is to test various hypotheses that could explain how an alteration in the circadian clock system could lead to changes in the phase of the sleep-wake cycle relative to the light-dark cycle. The objective of this project is to test the hypothesis that the altered circadian phase in ASPS or DSPS is due to an alteration in the way that the circadian clock responds to light.