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

研究人员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至15天而不知道时间。光照强度在100勒克斯以下。连续监测睡眠-觉醒节律和直肠温度节律。通过留置导管连续取血36小时，测定血浆褪黑素。在确定基线节律后，睡眠-觉醒时间表立即提前8小时，中间有一个通宵。通过固定1天、4天或7天的睡眠阶段诱导内部强制去同步，然后将受试者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-觉醒节律的夹带性。固定睡眠阶段为7天时，所有受试者保持睡眠节奏，固定睡眠阶段为4天时，一半受试者保持睡眠节奏。当睡眠阶段固定1天时，睡眠节奏完全不受影响。另一方面，即使固定了7天的睡眠阶段，血浆褪黑素和直肠温度的昼夜节律也没有被改变，但自由运行期受到显著影响。从这些结果来看，很明显，睡眠-觉醒节奏可以被社会时间线索所引导，但需要几天的短暂时间才能完全被引导。这种携带似乎不是由负责血浆褪黑激素和直肠温度的昼夜节律的振荡机制介导的。这些发现支持了人类生物钟由两个相互耦合且授时因子不同的自我维持振荡器组成的假设。

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.