Functional structure of human biological clock : Oscillation coupling and roles of melatonin in the two-oscillator model

在时间隔离设施下度过9至15天而不知道时间的健康男性受试者中分析昼夜节律以及睡眠。光照强度低于100勒克斯。连续监测睡眠-觉醒和直肠温度节律。通过留置导管连续采集血液36小时，并测定血浆褪黑激素。在确定基线节律后，立即将睡眠-觉醒时间表相位提前8小时，其间过夜。通过固定睡眠时相1、4或7天诱导受试者强制性内去兴奋，然后释放受试者进入自由奔跑状态，从自由奔跑睡眠节律的起始时相判断是否存在睡眠-觉醒节律的诱导。当睡眠相固定7天时，所有受试者的睡眠节律都被夹带，当固定4天时，有一半的受试者的睡眠节律被夹带。当睡眠相位仅固定1天时，睡眠节律根本不被诱导。另一方面，在血浆褪黑激素和直肠温度的昼夜节律没有夹带，即使当睡眠阶段是固定的7天，但自由运行期间显着affected.From这些结果，很明显，睡眠-觉醒节律可以夹带到社会时间线索，但需要几天的短暂，直到完全夹带。这种夹带似乎并不介导的振荡机制，负责在血浆褪黑激素和直肠温度的昼夜节律。这些发现支持了人类生物钟由两个相互耦合的自供振荡器组成的假设，这两个振荡器的授时钟是不同的。

Circadian rhythms as well as sleep were analyzed in healthy male subjects who spent 9 to 15 days without knowledge of time under temporal isolation facility. The light intensity was below 100 lux. The sleep-wake and rectal temperature rhythms were monitored continuously. Blood was sampled sequentially through an indwelling catether for 36 hours and plasma melatonin was determined. Immediately after the determination of baseline rhythms, the sleep-wake schedule was phase-advanced by 8 hours with an over night stay-up inbetween. Forced internal desynchronization was induced by fixing sleep phase either for l, 4 or 7 days, and then the subjects were released into free-run conditions.Entrainment of sleep-wake rhythm was judged from the initial phase of free-running sleep rhythm. The sleep rhythm was entrained in all subjects when the sleep phase was fixed for 7 days, and in half of subjects when fixed for 4 days. The sleep rhythm was not entrained at all when the sleep phase was fixed only for 1 days. On the other hand, the circadian rhythms in plasma melatonin and rectal temperature were not entrained even when the sleep phase was fixed for 7 days but the free-run periods were significantly affected.From these results, it becomes apparent that the sleep-wake rhythm can entrain to social time cues, but takes several days of transient until completely entrained. This entrainment does not seem to be mediated by the oscillation mechanism responsible for the ciracadian rhythms in plasma melatonin and rectal temperature. These findings support the hypothesis that the human biological clock consists of two self-sustained oscillators which are mutually coupled and whose zeitgebers are different.