Temporal Integration of Photoperiodic Signals in Mammals

描述(申请人提供)：本项目研究哺乳动物随着环境条件的变化而产生生理和行为特征的季节性变化的神经内分泌机制，以及这种变化对昼夜节律功能老化的影响。这一领域的研究考察了西伯利亚仓鼠、太阳穴仓鼠和叙利亚仓鼠分别在初夏和冬季的静态长日长和短日照下的反应。越来越多的证据表明，光周期系统在自然条件下的功能明显不同，这些系统在自然条件下进化的日长模式是递增的和连续变化的。对这些年节律的生态学相关理解在临床上尤其重要，因为人类就像实验室的啮齿动物一样，通常与日长的年度变化模式隔离开来，但这种剥夺的后果几乎没有得到检验。在仓鼠中的具体实验涉及1)在自然条件下褪黑素是否与内源性时间程序相互作用，这些程序调节光周期状态之间的转换；2)昼夜节律振荡器的功能如何受到季节性光周期的调节；3)与年龄相关的昼夜节律功能缺陷如何通过光周期操作来延缓。拟议的实验与理解之前已有文献记载的无数人类季节性节律有关(例如，在心血管疾病、神经发育障碍、免疫功能、睡眠时间、体重、抑郁和非精神情绪状态中)。此外，这些研究将评估光周期操作是否可能是实现人类节律快速相移的有效辅助手段，以及这种操作是否对老年人昼夜节律的扰乱具有治疗价值。最后，这些研究形成了必要的信息基础，以评估现代社会中人类经历的人工照明制度的潜在生理成本和好处。

DESCRIPTION (provided by applicant): This project investigates the neuroendocrine mechanisms by which mammals generate seasonal variations in physiological and behavioral traits in synchrony with changing environmental conditions and the consequences of this variation for aging of circadian function. Studies in this area have examined responses of Siberian, Phodopus sungorus, and Syrian hamsters, Mesocricetus auratus, exposed to static long and short day lengths of early summer and winter, respectively. Accumulating evidence establishes that photoperiodic systems function markedly differently under natural conditions that incorporate the incrementally and continuously changing pattern of day lengths under which these systems evolved. An ecologically relevant understanding of these annual rhythms is particularly important clinically, as humans, like laboratory rodents, are commonly isolated from the yearly pattern of change in daylength, but the consequences of this deprivation have gone virtually unexamined. Specific experiments in hamsters address 1) whether under naturalistic conditions melatonin interacts endogenous temporal programs that mediate the transitions between photoperiodic states; 2) how the function of the circadian oscillator is regulated by seasonal photoperiods; and 3) how age-related deficits in circadian function can be retarded by photoperiodic manipulations. The proposed experiments are relevant to an understanding of the myriad human seasonal rhythms that have been previously documented (e.g., in cardiovascular disease, neurodevelopmental disorders, immune function, sleep duration, body weight, depression and nonpsychiatric mood states). Additionally, these studies will assess whether photoperiodic manipulations might be effective adjuncts to achieve rapid phase-shifting of human rhythms, and whether such manipulations have therapeutic value for disruptions of circadian rhythmicity in old age. Finally, these studies form a necessary information base to evaluate the potential physiological costs and benefits of artificial lighting regimes experienced by humans in modern society.