The Circadian System: A Regulatory Feedback Network of Periphery and Brain

Abstract

Circadian rhythms are generated by the autonomous circadian clock, the suprachiasmatic nucleus (SCN), and clock genes that are present in all tissues. The SCN times these peripheral clocks, as well as behavioral and physiological processes. Recent studies show that frequent violations of conditions set by our biological clock, such as shift work, jet lag, sleep deprivation, or simply eating at the wrong time of the day, may have deleterious effects on health. This infringement, also known as circadian desynchronization, is associated with chronic diseases like diabetes, hypertension, cancer, and psychiatric disorders. In this review, we will evaluate evidence that these diseases stem from the need of the SCN for peripheral feedback to fine-tune its output and adjust physiological processes to the requirements of the moment. This feedback can vary from neuronal or hormonal signals from the liver to changes in blood pressure. Desynchronization renders the circadian network dysfunctional, resulting in a breakdown of many functions driven by the SCN, disrupting core clock rhythms in the periphery and disorganizing cellular processes that are normally driven by the synchrony between behavior and peripheral signals with neuronal and humoral output of the hypothalamus. Consequently, we propose that the loss of synchrony between the different elements of this circadian network as may occur during shiftwork and jet lag is the reason for the occurrence of health problems.

Suprachiasmatic Nucleus Interaction with the Arcuate Nucleus; Essential for Organizing Physiological Rhythms

“…This confirms the idea, also previously suggested (Webb et al, 2009; Hu et al, 2012; Buijs et al, 2016), that the SCN functions inside a larger circadian network of tightly linked oscillatory feedback circuits whose integral function is essential for regulating physiologic and behavioral functions. Long-term desynchronization within this circadian network due to changes in dietary habits, chronic jetlag, or shift work is known to contribute to pathology associated with “modern lifestyle,” such as hypertension, obesity, diabetes, and cancer (Scheer et al, 2010; Leproult et al, 2014; Kettner et al, 2016).…”

The systemic nature of CKD

“…Another major function of the nervous system in mammals is control of the circadian clock 227 . The suprachiasmatic nucleus in the hypothalamus is the central system that synchronizes peripheral systems 227 .…”

“…The suprachiasmatic nucleus in the hypothalamus is the central system that synchronizes peripheral systems 227 . Central and peripheral synchronizers share a common molecular clock that consists of self-sustained transcriptional and translational feedback loops 228 .…”

Relationship between Cognitive and Sleep–wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer’s Disease

“…Such areas are involved in the regulation of vegetative functions, including autonomic nervous system regulation and diurnal variation (Braak et al, 2011). Sleep–wake cycle regulation in particular, depends on intrinsic circadian rhythm generation by diencephalic structures, in addition to a series of environmental cues of sleep–wake cycle (Buijs et al, 2016). Thus, alterations in sleep could represent, in theory, early manifestations of late-onset AD (LOAD)-related neuropathological changes in the brain.…”