Adaptation to Jet Lag in Animal Models

动物模型对时差的适应

• 批准号: 7316340
• 负责人: JIMO BORJIGIN
• 金额: $ 30.52万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7316340
• 关键词: Address; Animal Model; Animals; Biological Clocks; Birds; Circadian Rhythms; Condition; Daily; Data; Disease; Disruption; Exhibits; Goals; Human; Individual; Investigation; Jet Lag Syndrome; Length; Life; Light; Lizards; Mammals; Measures; Melatonin; Motor Activity; Numbers; Pacemakers; Phase; Photoperiod; Process; Rate; Rattus; Research Personnel; Rodent; Role; Sleep; Sleep Deprivation; Symptoms; System; Temperature; Testing; Time; Travel; Variant; circadian pacemaker; coping; early onset; human study; insight; prevent; programs; shift work

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.

描述（由申请人提供）：昼夜节律每天由中央起搏器纳入 24 小时的环境明暗 (LD) 周期。 LD 周期变化（跨时区旅行时）、轮班工作以及睡眠不足后，所产生的节律会被打乱。人们普遍认识到，人类应对昼夜节律紊乱的方式存在巨大的个体差异。虽然有很多因素影响昼夜节律在这种破坏后重新恢复的速度，但尚不清楚昼夜节律系统的哪些参数决定了适应速度。使用松果体褪黑激素作为时钟标记，研究了啮齿类动物节律紊乱对新时区的适应情况。我们发现（1）重新进入延迟的 LD 循环是一个缓慢的过程； (2) 在近交系动物中，在夹带条件下，褪黑激素的起效时间存在较大的个体间差异； (3) 褪黑激素产生的时间是光周期（光周期长度）的函数； (4) 近交系大鼠 LD 周期延迟转移后，个体间的再夹带率存在较大差异。值得注意的是，我们发现褪黑激素产生的时间与重新产生的速度之间存在紧密的关联。在这项修订后的提案中，我们计划进一步研究啮齿类动物褪黑激素分泌时间与再夹带率之间的关系。目标 1 将检验以下假设：褪黑激素开始越早，动物在 LD 周期延迟转变后重新进入的速度就越快，无论转变的幅度如何。在目标 2 中，我们将确定啮齿类动物褪黑激素分泌的开始时间与固有周期之间的关系，并检验以下假设：昼夜节律周期越短，个体在 LD 周期延迟偏移后重新进入的速度就越快，无论偏移的大小如何。目标 3 将检查短光周期和长光周期下的重新夹带率与褪黑激素开始时间之间的关系，以检验以下假设：夜间时间越短，个体在 LD 周期延迟偏移后重新夹带的速度越快，无论偏移的大小如何。目标是在再夹带率和褪黑激素发作时间之间建立明确的关系。拟议的研究将影响我们对昼夜节律重新调整的基本理解，并将有助于我们理解人类如何应对昼夜节律紊乱，如时差、轮班工作和睡眠不足。