Stress and Circadian Rhythms

压力和昼夜节律

• 批准号: 6822765
• 负责人: THERESA M LEE
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6822765
• 关键词: Rodentias; cerebrospinal fluid; circadian rhythms; cortisol; functional ability; high performance liquid chromatography; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; melatonin; microdialysis; physiologic stressor; radioimmunoassay; suprachiasmatic nucleus

DESCRIPTION (provided by applicant): Essentially all multicellular organisms demonstrate circadian rhythms of physiology and behavior. These rhythms maintain synchrony (via specific phase relationships) between the organism and the outside world, as well as internal synchrony between physiological functions. A rapid change in the light:dark cycle alters the phase relationship between the organism and the outside world, typically requiring days to weeks for full recovery, during which time the internal synchrony of the individual is disordered. In humans, this phenomenon is referred to as jet lag and has been linked to physical, emotional, and psychiatric problems such as ulcers, depression, and emotional distress. It is common in shift workers and long-distance travelers. This proposal explores the possibility that the delay in recovery of internal and external circadian synchrony in mammals (reflected in activity and cortisol rhythms), as compared with the recovery of melatonin entrainment (thought to best reflect SCN function), is in part due to the activation of the hypothalamic-pituitary-adrenal axis (stress axis) as a result of the shifted light cycle. We hypothesize that the central circadian mechanism, as reflected in the melatonin rhythm, re-entrains faster than activity or cortisol rhythms, and that melatonin rhythm re-entrainment is independent of the stress axis. Secondarily, we expect that manipulating the stress axis so as to elevate or reduce stress will concomitantly increase or delay recovery rates of activity and cortisol rhythms after phase shifts, but that melatonin re-entrainment will be unaffected. To test these hypotheses we will use microdialysis to measure cortisol and melatonin at hourly intervals while avoiding the blood-loss problems for a small mammal. Specific Aim 1 will determine the relationship between re-entrainment rate and cortisol concentrations and/or circadian cortisol rhythm in a series of 4 experiments which independently manipulate entrainment rate or cortisol levels while measuring the other variable. Specific Aim 2 will determine the relationship between melatonin, cortisol and activity rhythms during re-entrainment to test the hypothesis that melatonin rhythm, and therefore the central oscillator mechanism, recovers more rapidly than other rhythms. Providing a better understanding of the interactions between stress and the circadian system will allow for a more thorough investigation of the pathology of desynchronized circadian rhythms and may lead to treatments to reduce the desynchrony.

描述（由申请人提供）：本质上，所有多细胞生物都表现出生理和行为的昼夜节律。这些节奏保持生物体与外界之间的同步（通过特定的阶段关系），以及生理功能之间的内部同步。光的快速变化：黑暗循环改变了生物体与外界之间的相位关系，通常需要数天到几周才能完全恢复，在此期间，个体的内部同步是无序的。在人类中，这种现象被称为喷气滞后，与身体，情感和精神病问题（例如溃疡，抑郁和情绪困扰）有关。它在轮班工人和长途旅行者中很常见。该提案探讨了与褪黑激素夹带的恢复（认为可以最好地反映SCN功能）相比，哺乳动物内部和外部昼夜节律同步的恢复延迟（反映在活动和皮质醇节奏中）的可能性，部分是由于下丘脑 - 甲状腺刺激性辅助轴心的激活（应力轴心轴）的循环循环。我们假设在褪黑激素节奏中反映的中央昼夜节律机制比活性或皮质醇节奏更快，并且褪黑激素节奏的再入剂与应力轴无关。其次，我们希望操纵应力轴以升高或减轻压力将同时提高或延迟相移后的活动恢复率和皮质醇节奏的恢复速率，但是这种褪黑激素的再植入将不受影响。为了检验这些假设，我们将使用微透析以每小时的间隔来测量皮质醇和褪黑激素，同时避免小型哺乳动物的血液损失问题。具体目标1将在一系列4个实验中，确定重新入口率与皮质醇浓度与/或昼夜节律皮质醇节律之间的关系，这些实验独立操纵夹带率或皮质醇水平，同时测量其他可变。具体的目标2将确定褪黑激素，皮质醇和活性节奏在重新入学期间的关系，以检验褪黑激素节奏及其中心振荡器机制的假设比其他节奏更快地恢复。对压力与昼夜节律系统之间的相互作用有更好的了解将使对异步的昼夜节律的病理进行更彻底的研究，并可能导致治疗以减少脱节。