LIGHT-INDUCED SUPPRESSION OF MELATONIN IN ADVANCED AND DELAYED SLEEP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在过去的几年里，在揭示哺乳动物昼夜节律产生的分子基础方面取得了很大的进展。这些对啮齿动物和苍蝇的分子研究刺激了对基因差异的搜索，这些差异可能是人类昼夜节律改变和/或睡眠障碍的基础。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，这两种疾病被归类为睡眠相延迟综合症(DSPS)和晚期睡眠相综合症(ASPS)。DSPs的特点是在凌晨2点到6点之前持续无法入睡，在10点到1点之前难以醒来，而ASPS的特点是习惯性和非自愿的睡眠和醒来时间至少比社会平均水平早几个小时。最常见的主诉是下午晚些时候或晚上昏昏欲睡，凌晨2-5点醒来基于对大家庭的研究，最近有两个报告表明，ASPS和DSPs都有遗传基础，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所致。此外，最近对散发性DSPs的一项研究表明，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的遗传学基础的研究为阐明睡眠-觉醒和生物钟系统如何相互整合，以及特定的生物钟基因的改变如何导致睡眠和觉醒的时间改变提供了一条新的令人兴奋的途径，但我们对导致这些昼夜睡眠障碍的生理机制的了解实际上是相当有限的。NIH母公司资助的基金的目标之一是测试各种假说，这些假说可以解释生物钟系统的变化如何导致睡眠-觉醒周期相对于光明-黑暗周期的阶段发生变化。这个项目的目标是检验这样一种假设，即ASPS或DSPs中昼夜节律的变化是由于生物钟对光的反应方式发生了变化。

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.