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

分析了健康男性受试者的昼夜节律和睡眠，这些受试者在时间隔离设施中度过了9到15天而不知道时间。光强在100勒克斯以下。持续监测睡眠-觉醒和直肠温度节律。留置儿茶醚连续采血36小时，测定血浆褪黑素。在确定了基线节律后，立即将睡眠-醒来时间表提前了8小时，其间有一整晚的熬夜。通过固定睡眠时相诱发强迫内去同步化，时间分别为4天和7天，然后释放到自由运行状态，从自由运行睡眠节律的初始阶段判断睡眠-觉醒节律的启动。睡眠时相固定为7天时，所有受试者的睡眠节律都受到了影响，而固定睡眠时相为4天时，有一半受试者的睡眠节律被改变。睡眠时相固定1d，睡眠节律完全不受影响。另一方面，即使睡眠时间固定为7天，血浆褪黑素和直肠温度的昼夜节律也没有受到影响，但自由奔跑周期受到了显著影响。从这些结果可以看出，睡眠-觉醒节律可以影响社交时间提示，但需要几天的短暂时间才能完全影响。这种夹带似乎不是由引起血浆褪黑素和直肠温度昼夜节律的振荡机制所调节的。这些发现支持这样一种假设，即人类的生物钟由两个相互耦合的自持振荡器组成，它们的时标是不同的。

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.