Different levels of circadian (de)synchrony ­– where does it hurt?

Abstract

A network of cellular timers ensures the maintenance of homeostasis by temporal modulation of physiological processes across the day. These so-called circadian clocks are synchronized to geophysical time by external time cues (or zeitgebers). In modern societies, natural environmental cycles are disrupted by artificial lighting, around-the-clock availability of food or shiftwork. Such contradictory zeitgeber input promotes chronodisruption, i.e., the perturbation of internal circadian rhythms, resulting in adverse health outcomes. While this phenomenon is well described, it is still poorly understood at which level of organization perturbed rhythms impact on health and wellbeing. In this review, we discuss different levels of chronodisruption and what is known about their health effects. We summarize the results of disrupted phase coherence between external and internal time vs. misalignment of tissue clocks amongst each other, i.e., internal desynchrony. Last, phase incoherence can also occur at the tissue level itself. Here, alterations in phase coordination can emerge between cellular clocks of the same tissue or between different clock genes within the single cell. A better understanding of the mechanisms of circadian misalignment and its effects on physiology will help to find effective tools to prevent or treat disorders arising from modern-day chronodisruptive environments.

Epileptogenesis Inhibits the Circadian Clock and Reshapes the Diurnal Transcriptomic Rhythmicity in the Mouse Hippocampus

“…The deletion of Bmal1 in mice, but not other clock genes, is associated with the circadian behavior pattern abolishment 20 . These central clock networks can be synchronized by environmental temporal cues, such as light, also known as Zeitgeber time (ZT; the German word for 'time giver') 21,22 . Pre-clinical and clinical evidence suggests that the abnormal expression of BMAL1 may be involved in the pathogenesis of epilepsy [23][24][25] .…”