Gronfier Claude, Wright Kenneth P, Kronauer Richard E, Czeisler Charles A
Division of Sleep Medicine, Department of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2007 May 22;104(21):9081-6. doi: 10.1073/pnas.0702835104. Epub 2007 May 14.
Entrainment of the circadian pacemaker to the light:dark cycle is necessary for rhythmic physiological functions to be appropriately timed over the 24-h day. Nonentrainment results in sleep, endocrine, and neurobehavioral impairments. Exposures to intermittent bright light pulses have been reported to phase shift the circadian pacemaker with great efficacy. Therefore, we tested the hypothesis that a modulated light exposure (MLE) with bright light pulses in the evening would entrain subjects to a light:dark cycle 1 h longer than their own circadian period (tau). Twelve subjects underwent a 65-day inpatient study. Individual subject's circadian period was determined in a forced desynchrony protocol. Subsequently, subjects were released into 30 longer-than-24-h days (daylength of tau + 1 h) in one of three light:dark conditions: (i) approximately 25 lux; (ii) approximately 100 lux; and (iii) MLE: approximately 25 lux followed by approximately 100 lux, plus two 45-min bright light pulses of approximately 9,500 lux near the end of scheduled wakefulness. We found that lighting levels of approximately 25 lux were insufficient to entrain all subjects tested. Exposure to approximately 100 lux was sufficient to entrain subjects, although at a significantly wider phase angle compared with baseline. Exposure to MLE was able to entrain the subjects to the imposed sleep-wake cycles but at a phase angle comparable to baseline. These results suggest that MLE can be used to entrain the circadian pacemaker to non-24-h days. The implications of these findings are important because they could be used to treat circadian misalignment associated with space flight and circadian rhythm sleep disorders such as shift-work disorder.
使昼夜节律起搏器与明暗周期同步对于节律性生理功能在24小时一天中得到适当定时是必要的。不同步会导致睡眠、内分泌和神经行为障碍。据报道,暴露于间歇性强光脉冲能有效地使昼夜节律起搏器发生相位移动。因此,我们测试了这样一个假设:在晚上给予强光脉冲的调制光暴露(MLE)能使受试者与比他们自身昼夜周期(tau)长1小时的明暗周期同步。12名受试者接受了一项为期65天的住院研究。通过强制去同步方案确定个体受试者的昼夜周期。随后,受试者在以下三种明暗条件之一中被置于30个长于24小时的天数(昼长为tau + 1小时):(i)约25勒克斯;(ii)约100勒克斯;以及(iii)MLE:约25勒克斯接着约100勒克斯,再加上在预定清醒结束时两个约9500勒克斯的45分钟强光脉冲。我们发现约25勒克斯的光照水平不足以使所有受试对象同步。暴露于约100勒克斯足以使受试者同步,尽管与基线相比相位角显著更宽。暴露于MLE能够使受试者与强加的睡眠 - 觉醒周期同步,但相位角与基线相当。这些结果表明,MLE可用于使昼夜节律起搏器与非24小时的天数同步。这些发现的意义重大,因为它们可用于治疗与太空飞行相关的昼夜节律失调以及昼夜节律睡眠障碍,如轮班工作障碍。