Temporal Integration of Photoperiodic Signals in Mammals

描述（由申请人提供）：本项目研究哺乳动物生理和行为特征随环境条件变化而产生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衰老的影响。该地区的研究分别检测了西伯利亚仓鼠、阳光足鼠和叙利亚中天仓鼠（Mesocricetus auratus）在初夏和冬季暴露于静态长昼和短昼的反应。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，这些自然条件包含了这些系统进化的日长增量和连续变化的模式。对这些年度节律的生态学相关理解在临床上尤为重要，因为人类，就像实验室的啮齿动物一样，通常与白昼长度的年度变化模式隔离开来，但这种剥夺的后果实际上没有得到检验。在仓鼠中进行的特定实验解决了1)在自然条件下褪黑激素是否与介导光周期状态之间转换的内源性时间程序相互作用；2)昼夜节律振荡器的功能如何受季节光周期的调控；3)如何通过光周期操作延缓与年龄相关的昼夜节律功能缺陷。拟议的实验与先前记录的无数人类季节性节律（例如，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）的理解有关。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昼夜节律中断具有治疗价值。最后，这些研究为评估人类在现代社会中所经历的人工照明制度的潜在生理成本和收益提供了必要的信息基础。

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.