Adaptation to Jet Lag in Animal Models

动物模型对时差的适应

• 批准号: 7414366
• 负责人: JIMO BORJIGIN
• 金额: $ 33.25万
• 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/7414366
• 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）：昼夜节律通过中央起搏器每天进入24小时的环境光暗（LD）周期。随着LD周期的变化（跨时区旅行时）、轮班工作和睡眠剥夺，所带的节奏会被打乱。人们普遍认为，人类如何应对昼夜节律的中断存在很大的个体间差异。虽然有很多因素决定了在这种中断之后，昼夜节律重新恢复的速度有多快，但尚不清楚昼夜节律计时系统的哪些参数决定了适应的速度。利用松果体褪黑素作为时钟标记，研究了啮齿动物对新时区节律的适应。我们发现：(1)延迟LD周期的重携是一个缓慢的过程；(2)远交种动物在受胁迫条件下褪黑激素的起效时间存在较大的个体间差异；(3)褪黑素起效的时间是光周期（光周期长度）的函数；(4)远交种大鼠在LD周期延迟转移后的再携带率存在较大的个体间差异。值得注意的是，我们已经发现了褪黑激素开始的时间和复带率之间的紧密联系。在本次修订的提案中，我们计划进一步研究褪黑激素分泌时间与啮齿动物再娱乐率之间的关系。目的1将检验这一假设，即褪黑激素开始的越早，动物在LD周期延迟转移后重新训练的速度越快，无论转移的幅度如何。在Aim 2中，我们将确定褪黑激素分泌的开始时间与啮齿动物的内在周期之间的关系，并验证昼夜节律周期越短，个体在LD周期延迟转移后恢复得越快的假设，无论转移的幅度如何。目的3将检验在短光周期和长光周期中再吸收速率和褪黑激素开始时间之间的关系，以检验一个假设，即夜周期越短，个体在LD周期延迟转移后再吸收速度越快，无论转移的幅度如何。目的是建立一个明确的关系之间的再伴流率和褪黑激素开始的时间。拟议的研究将影响我们对昼夜节律再调节的基本理解，并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。