Department of Physiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Am J Physiol Regul Integr Comp Physiol. 2024 Jan 1;326(1):R19-R28. doi: 10.1152/ajpregu.00094.2023. Epub 2023 Oct 23.
The sleep-wake cycle of human subjects was artificially split into two episodes by imposing an 8-h light and 4-h dark cycle (LD 8:4) twice a day for 7 days, which was followed by a 3-day free-running session. Sleep was permitted only in the dark period. The subjects in the ordinary group were exposed to ordinary light (ca. 500 lx) in the 8-h light period, and those in the bright light group to bright (ca. 5,000 lx) and ordinary light alternatively with bright light after the first dark period (2400-400). Split sleeps persisted in the free-running session with the major episode around the first dark period and the minor episode around the second dark period. By contrast, circadian melatonin rhythm in the free-running session significantly phase delayed in the ordinary light group, but phase advanced in the bright light group, keeping the melatonin rhythm unsplit. The length of nocturnal melatonin secretion (NMS) was significantly shortened in the bright light group. Interestingly, the falling phase of NMS advanced significantly further than the rising phase. Such a difference was not detected in the ordinary light group. Similar differences were observed in the body temperature rhythm. These findings indicated oscillatory mechanisms underlying split sleeps distinct from the circadian pacemaker and suggested an involvement of different circadian oscillators in the rising and falling phases of NMS, which is consistent with the dual oscillator model proposed for the circadian system of nocturnal rodents. The present study demonstrated that human sleep was separated into two essentially identical components, which persisted under constant conditions, suggesting circadian oscillator underlying split-sleep episodes. The study also indicated differential light sensitivities in the rising and falling phases of circadian melatonin rhythm, indicating the involvement of two different oscillators. These results consisted of the evening and morning dual-oscillator hypothesis for the circadian pacemaker and the hierarchical model for the pacemaker and sleep-wake cycle.
人类受试者的睡眠-觉醒周期通过每天两次施加 8 小时光照和 4 小时黑暗循环（LD 8:4）人为地分为两个时段，持续 7 天，随后进行 3 天的自由运行期。只有在黑暗期才允许睡眠。普通组的受试者在 8 小时的光照期接受普通光照（约 500 lx），而明亮光照组的受试者则在第一黑暗期后（2400-400）交替接受明亮（约 5,000 lx）和普通光照。在自由运行期间，分裂睡眠持续存在，主要时段在第一个黑暗期周围，次要时段在第二个黑暗期周围。相比之下，在自由运行期间，普通光照组的褪黑素节律明显相位延迟，而明亮光照组的相位提前，使褪黑素节律不分裂。明亮光照组的夜间褪黑素分泌（NMS）时间明显缩短。有趣的是，NMS 的下降阶段比上升阶段提前得更明显。在普通光照组中没有检测到这种差异。体温节律也观察到类似的差异。这些发现表明，分裂睡眠的振荡机制与昼夜节律起搏器不同，并表明不同的昼夜振荡器参与 NMS 的上升和下降阶段，这与提出的夜间啮齿动物昼夜节律系统的双振荡器模型一致。本研究表明，人类睡眠被分为两个基本相同的成分，在恒常条件下持续存在，这表明昼夜振荡器是分裂睡眠的基础。该研究还表明，昼夜褪黑素节律的上升和下降阶段的光敏感性不同，表明涉及两个不同的振荡器。这些结果包括昼夜节律起搏器的傍晚和清晨双振荡器假说以及起搏器和睡眠-觉醒周期的分层模型。
