Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
J Biol Rhythms. 2019 Feb;34(1):105-110. doi: 10.1177/0748730418820727. Epub 2018 Dec 31.
Artificial lab manipulation of LD cycles has enabled simulations of the disruptive conditions found in modern human societies, such as jet-lag, night-work and light at night. New techniques using animal models have been developed, and these can greatly improve our understanding of circadian disruption. Some of these techniques, such as in vivo bioluminescence assays, require minimum external light. This requirement is challenging because the usual lighting protocols applied in circadian desynchronization experiments rely on considerable light input. Here, we present a novel LD regimen that can disrupt circadian rhythms with little light per day, based on computer simulations of a model limit-cycle oscillator. The model predicts that a single light pulse per day has the potential to disturb rhythmicity when pulse times are randomly distributed within an interval. Counterintuitively, the rhythm still preserves an underlying 24-h periodicity when this interval is as large as 14 h, indicating that day/night cues are still detectable. Only when pulses are spread throughout the whole 24-h day does the rhythm lose any day-to-day period correlation. In addition, the model also reveals that stronger pulses of brighter light should exacerbate the disrupting effects. We propose the use of this LD schedule-which would be compatible with the requirements of in vivo bioluminescence assays-to help understand circadian disruption and associated illnesses.
人工实验室操纵 LD 周期使人们能够模拟现代人类社会中存在的扰乱条件,如时差、夜班和夜间光照。已经开发出了使用动物模型的新技术,这些技术可以极大地提高我们对昼夜节律紊乱的理解。其中一些技术,如体内生物发光测定法,需要最小的外部光照。这一要求具有挑战性,因为在昼夜节律去同步实验中应用的常规照明方案依赖于相当大的光照输入。在这里,我们根据模型限幅振荡器的计算机模拟,提出了一种新的 LD 方案,该方案每天只需少量光照即可扰乱昼夜节律。该模型预测,当每天的光脉冲时间在一个间隔内随机分布时,单个光脉冲有可能扰乱节律性。反直觉的是,当这个间隔大到 14 小时时,节律仍然保持着潜在的 24 小时周期性,表明昼夜线索仍然可以被检测到。只有当脉冲分布在整个 24 小时周期内时,节律才会失去任何日常的周期相关性。此外,该模型还揭示了更强的、更亮的脉冲光应该会加剧扰乱效应。我们建议使用这种 LD 方案,该方案与体内生物发光测定法的要求兼容,以帮助理解昼夜节律紊乱和相关疾病。