Adaptation to Jet Lag in Animal Models

描述（由申请人提供）：通过中枢起搏器每天将昼夜节律带入24小时的环境亮-暗（LD）周期。在LD周期的移位（当跨越时区时）、轮班工作和睡眠剥夺之后，夹带的节律被破坏。人们普遍认为，人类如何科普昼夜节律的破坏存在很大的个体差异。虽然有大量的因素有助于如何快速的昼夜节律重新牵引后，这种中断，它是不知道什么参数的昼夜节律定时系统确定的适应率。利用松果体褪黑激素作为生物钟标记，研究了啮齿类动物对新时区节律紊乱的适应。我们发现：（1）延迟的LD周期的再夹带是一个缓慢的过程;（2）远交系动物在夹带条件下褪黑激素起始时间存在很大的个体间差异;（3）褪黑激素起始时间是光周期的函数（光周期的长度）;和（4）一个大的个体间差异存在于率的再夹带后，在远交大鼠的LD周期的延迟移位。值得注意的是，我们已经发现了褪黑激素发作的时间和再夹带率之间的紧密联系。在这个修订后的建议，我们计划进一步调查褪黑激素分泌的时间和啮齿动物的再夹带率之间的关系。目的1将测试的假设，即褪黑激素发作越早，更快的动物reentrain以下延迟移位的LD周期，无论移位的幅度。在目标2中，我们将确定褪黑激素分泌的起始时间和啮齿动物的固有周期之间的关系，并检验假设，即昼夜节律周期越短，个体在LD周期延迟移位后的再牵引速度越快，而不管移位的幅度如何。目的3将检查在短和长光周期中褪黑激素发作的时间和再夹带率之间的关系，以检验以下假设：即夜间时间越短，LD周期延迟移位后个体再夹带越快，而不管移位的幅度如何。我们的目标是建立一个明确的再夹带率和褪黑激素发作的时间之间的关系。拟议中的研究将影响我们对昼夜节律再诱导的基本理解，并将有助于我们了解人类如何科普昼夜节律中断，如时差，轮班工作和睡眠剥夺。

DESCRIPTION (provided by applicant): Circadian rhythms are entrained daily to the environmental light-dark (LD) cycle of 24h by a central pacemaker. The entrained rhythms are disrupted following a shift of the LD cycle (when traveling across time zones), in shiftwork, and following sleep deprivations. It is widely recognized that large inter-individual variations exist in how humans cope with disruptions of circadian rhythms. While a large number of factors contribute to how fast circadian rhythms reentrain following such disruptions, it is not known what parameters of the circadian timing system determine the rate of adaptation. Adaptation of disrupted rhythms to a new time zone was investigated in rodents using pineal melatonin as a clock marker. We have found that (1) reentrainment to a delayed LD cycle is a slow process; (2) a large inter-individual variation exists in timings of melatonin onset under entrained conditions in outbred animals; (3) the timing of melatonin onset is a function of photoperiod (length of the light period); and (4) a large inter-individual variation exists in rate of reentrainment following a delay shift of the LD cycle in outbred rats. Remarkably, we have discovered a tight association between the timing of melatonin onset and the rate of reentrainment. In this revised proposal, we plan to further investigate the relationship between timings of melatonin secretion and rate of reentrainment in rodents. Aim 1 will test the hypothesis that the earlier the melatonin onset, the faster animals reentrain following a delay shift of the LD cycle, regardless the magnitude of the shift. In Aim 2, we will determine the relationship between onset timings of melatonin secretion and intrinsic period of rodents and test the hypothesis that shorter the circadian period, faster the individual reentrains following a delay shift of the LD cycle, regardless the magnitude of the shift. Aim 3 will examine the relationship between rate of reentrainment and timing of melatonin onset in both short and long photoperiod to test the hypothesis that the shorter the night period, the faster the individual reentrains following a delay shift of the LD cycle, regardless the magnitude of the shift. The goal is to establish an unambiguous relationship between the rate of reentrainment and timing of melatonin onset. The proposed studies will impact our basic understanding of circadian rhythm reentrainment, and will benefit our understanding of how humans cope with circadian disruptions such as jet lag, shift work, and sleep deprivations.