Grabe Saskia, Mahammadov Elmir, Olmo Marta Del, Herzel Hanspeter
CharitéCenter for Basic Sciences, Institute for Theoretical Biology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Stem Cell Center (SCC), Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, Munich, Germany.
Front Netw Physiol. 2022 Jan 18;1:803011. doi: 10.3389/fnetp.2021.803011. eCollection 2021.
Circadian rhythms are biological rhythms with a period close to 24 h. They become entrained to the Earth's solar day different periodic cues, so-called zeitgebers. The entrainment of circadian rhythms to a single zeitgeber was investigated in many mathematical clock models of different levels of complexity, ranging from the Poincaré oscillator and the Goodwin model to biologically more detailed models of multiple transcriptional translational feedback loops. However, circadian rhythms are exposed to multiple coexisting zeitgebers in nature. Therefore, we study synergistic effects of two coexisting zeitgebers on different components of the circadian clock. We investigate the induction of genes by light together with modulations of nuclear receptor activities by drugs and metabolism. Our results show that the entrainment of a circadian rhythm to two coexisting zeitgebers depends strongly on the phase difference between the two zeitgebers. Synergistic interactions of zeitgebers can strengthen diurnal rhythms to reduce detrimental effects of shift-work and jet lag. Medical treatment strategies which aim for stable circadian rhythms should consider interactions of multiple zeitgebers.
昼夜节律是周期接近24小时的生物节律。它们通过不同的周期性线索（即所谓的授时因子）与地球的太阳日同步。在许多不同复杂程度的数学时钟模型中研究了昼夜节律与单一授时因子的同步，这些模型从庞加莱振荡器和古德温模型到生物学上更详细的多个转录翻译反馈环模型。然而，昼夜节律在自然界中会受到多种共存授时因子的影响。因此，我们研究了两种共存授时因子对生物钟不同组成部分的协同作用。我们研究了光对基因的诱导以及药物和代谢对核受体活性的调节。我们的结果表明，昼夜节律与两种共存授时因子的同步在很大程度上取决于这两种授时因子之间的相位差。授时因子的协同相互作用可以加强昼夜节律，以减少轮班工作和时差反应的有害影响。旨在维持稳定昼夜节律的医学治疗策略应考虑多种授时因子的相互作用。
