Pfeffer Martina, Korf Horst-Werner, von Gall Charlotte
Dr. Senckenbergische Anatomie, Institut für Anatomie II, Fachbereich Medizin, Goethe-Universität , Frankfurt/Main , Germany .
Chronobiol Int. 2015 Feb;32(1):81-91. doi: 10.3109/07420528.2014.956218. Epub 2014 Sep 12.
Behavior, physiological functions and cognitive performance change over the time of the day. These daily rhythms are either externally driven by rhythmic environmental cues such as the light/dark cycle (masking) or controlled by an internal circadian clock, the suprachiasmatic nucleus (SCN), which can be entrained to the light/dark cycle. Within a given species, there is genetically determined variability in the temporal preference for the onset of the active phase, the chronotype. The chronotype is the phase of entrainment between external and internal time and is largely regulated by the circadian clock. Genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population. However, little is known about the determination of the chronotype, the stability of the locomotor rhythm and the re-synchronization capacity to jet lag in an animal without a functional endogenous clock. Therefore, we analyzed the chronotype of BMAL1-deficient mice (BMAL1-/-) as well as the effects of repeated experimental jet lag on locomotor activity rhythms. Moreover, light-induced period expression in the retina was analyzed to assess the responsiveness of the circadian light input system. In contrast to wild-type mice, BMAL1-/- showed a significantly later chronotype, adapted more rapidly to both phase advance and delay but showed reduced robustness of rhythmic locomotor activity after repeated phase shifts. However, photic induction of Period in the retina was not different between the two genotypes. Our findings suggest that a disturbed clockwork is associated with a late chronotype, reduced rhythm stability and higher vulnerability to repeated external desynchronization.
行为、生理功能和认知表现会随着一天中的时间而变化。这些日常节律要么由有节律的环境线索（如光/暗周期）外部驱动（掩盖作用），要么由内部生物钟——视交叉上核（SCN）控制，该生物钟可与光/暗周期同步。在给定物种内，活动期开始的时间偏好存在基因决定的变异性，即昼夜节律类型。昼夜节律类型是外部时间和内部时间之间的同步阶段，很大程度上由生物钟调节。生物钟基因的遗传变异和环境影响导致了给定人群中昼夜节律类型的分布。然而，对于没有功能性内源性生物钟的动物，昼夜节律类型的确定、运动节律的稳定性以及对时差的重新同步能力知之甚少。因此，我们分析了BMAL1基因缺陷小鼠（BMAL1-/-）的昼夜节律类型以及重复实验性时差对运动活动节律的影响。此外，还分析了视网膜中光诱导的周期蛋白表达，以评估昼夜光输入系统的反应性。与野生型小鼠相比，BMAL1-/-表现出明显更晚的昼夜节律类型，对相位提前和延迟的适应都更快，但在重复相位转移后，其节律性运动活动的稳健性降低。然而，两种基因型之间视网膜中周期蛋白的光诱导没有差异。我们的研究结果表明，生物钟紊乱与较晚的昼夜节律类型、降低的节律稳定性以及对反复外部去同步化的更高易感性有关。
