The mammalian circadian system: a hierarchical multi-oscillator structure for generating circadian rhythm

The circadian rhythm of glucocorticoids has long been recognised within the last 75 years. Since the beginning, researchers have sought to identify basic mechanisms underlying the origin and emergence of the corticosteroid circadian rhythmicity among mammals. Accordingly, Young, Hall and Rosbash, laureates of the 2017 Nobel Prize in Physiology or Medicine, as well as Takahashi’s group among others, have characterised the molecular cogwheels of the circadian system, describing interlocking transcription/translation feedback loops essential for normal circadian rhythms. Plasma glucocorticoid circadian variation depends on the expression of intrinsic clock genes within the anatomic components of the hypothalamic–pituitary–adrenal axis, which are organised in a hierarchical manner. This review presents a general overview of the glucocorticoid circadian clock mechanisms, highlighting the ontogeny of the pituitary–adrenal axis diurnal rhythmicity as well as the involvement of circadian rhythm abnormalities in the physiopathology and diagnosis of Cushing’s disease.

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3. When timing goes wrong

Circadian Rhythms: A Very Short Introduction ◽

10.1093/actrade/9780198717683.003.0003 ◽

2017 ◽

pp. 24-44

Author(s):

Russell G. Foster ◽

Leon Kreitzman

Keyword(s):

Circadian Rhythm ◽

Time Of Day ◽

Circadian System ◽

Multiple Time ◽

Sleep Phase ◽

Circadian Rhythm Sleep Disorders ◽

Time Zones ◽

Delayed Sleep Phase Disorder ◽

Delayed Sleep Phase ◽

Delayed Sleep

While time of day, interacting with an individual’s chronotype, can have an important impact upon performance and health, severe disruption of the circadian system adds another level of complexity and severity. ‘When timing goes wrong’ considers the effects of flying across multiple time zones, resulting in jet lag, and shift work on human health. Sleep and circadian rhythm disruption is almost always associated with poor health. Four circadian rhythm sleep disorders have been identified: advanced sleep phase disorder, delayed sleep phase disorder, freerunning, and irregular sleep timing. Sleep and circadian rhythm disruption in mental illness and neurodegenerative disease is also discussed.

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Chronic centrifugation (hypergravity) disrupts the circadian system of the rat

Journal of Applied Physiology ◽

10.1152/japplphysiol.00707.2002 ◽

2003 ◽

Vol 95 (3) ◽

pp. 1266-1278 ◽

Cited By ~ 15

Author(s):

D. C. Holley ◽

C. W. DeRoshia ◽

M. M. Moran ◽

C. E. Wade

Keyword(s):

Circadian Rhythm ◽

Time Course ◽

Control Period ◽

Circadian System ◽

Deep Body Temperature ◽

Periodicity Analysis ◽

Time Required ◽

Dose Dependent ◽

Deep Body ◽

Percent Decrease

The present study was conducted to evaluate the response of rat deep body temperature (DBT) and gross locomotor activity (LMA) circadian rhythms to acute hypergravity onset and adaptation to chronic (14 day) hypergravity exposure over three gravity intensities (1.25, 1.5, and 2 G). Centrifugation of unanesthetized naive animals resulted in a dramatic acute decrease in DBT (-1.45, -2.40, and -3.09°C for the 1.25, 1.5, and 2.0 G groups, respectively). LMA was suppressed for the duration of centrifugation (vs. control period); the percent decrease for each group on days 12-14, respectively, was 1.0 G, -15.2%, P = not significant; 1.25 G, -26.9%, P < 0.02; 1.5 G, -44.5%, P < 0.01; and 2.0 G, -63.1%, P < 0.002. The time required for DBT and LMA circadian rhythmic adaptation and stabilization to hypergravity onset increased from 1.25 to 2.0 G in all circadian metrics except daily means. Periodicity analysis detected the phenomenon of circadian rhythm splitting, which has not been reported previously in response to chronic hypergravity exposure. Our analysis documents the disruptive and dose-dependent effects of hypergravity on circadian rhythmicity and the time course of adaptation to 14-day chronic centrifugation exposure.

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Chronobiology Revisited in Psychiatric Disorders: From a Translational Perspective

Psychiatry Investigation ◽

10.30773/pi.2020.0129 ◽

2020 ◽

Vol 17 (8) ◽

pp. 725-743 ◽

Cited By ~ 1

Author(s):

Simge Seren Kirlioglu ◽

Yasin Hasan Balcioglu

Keyword(s):

Circadian Rhythm ◽

Mental Disorders ◽

Psychiatric Disorders ◽

Mood Disorders ◽

Psychotic Disorders ◽

Neural Substrates ◽

Circadian System ◽

Circadian Physiology ◽

Study Designs ◽

Lines Of Evidence

Objective Several lines of evidence support a relationship between circadian rhythms disruption in the onset, course, and maintenance of mental disorders. Despite the study of circadian phenotypes promising a decent understanding of the pathophysiologic or etiologic mechanisms of psychiatric entities, several questions still need to be addressed. In this review, we aimed to synthesize the literature investigating chronobiologic theories and their associations with psychiatric entities.Methods The Medline, Embase, PsycInfo, and Scopus databases were comprehensively and systematically searched and articles published between January 1990 and October 2019 were reviewed. Different combinations of the relevant keywords were polled. We first introduced molecular elements and mechanisms of the circadian system to promote a better understanding of the chronobiologic implications of mental disorders. Then, we comprehensively and systematically reviewed circadian system studies in mood disorders, schizophrenia, and anxiety disorders.Results Although subject characteristics and study designs vary across studies, current research has demonstrated that circadian pathologies, including genetic and neurohumoral alterations, represent the neural substrates of the pathophysiology of many psychiatric disorders. Impaired HPA-axis function-related glucocorticoid rhythm and disrupted melatonin homeostasis have been prominently demonstrated in schizophrenia and other psychotic disorders, while alterations of molecular expressions of circadian rhythm genes including <i>CLOCK, PER</i>, and <i>CRY</i> have been reported to be involved in the pathogenesis of mood disorders.Conclusion Further translational work is needed to identify the causal relationship between circadian physiology abnormalities and mental disorders and related psychopathology, and to develop sound pharmacologic interventions.

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Light-induced uncoupling of multioscillatory circadian system in a diurnal rodent, Asian chipmunk

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.5.r1390 ◽

1999 ◽

Vol 276 (5) ◽

pp. R1390-R1396 ◽

Cited By ~ 11

Author(s):

Sato Honma ◽

Ken-Ichi Honma

Keyword(s):

Circadian Rhythm ◽

Light Pulse ◽

Response Curve ◽

Phase Response Curve ◽

Circadian System ◽

Locomotor Rhythm ◽

Subjective Night ◽

Large Phase ◽

Activity Band ◽

Oscillatory Coupling

Responses of the circadian locomotor rhythm to a single light pulse were examined in a diurnal rodent, Asian chipmunk, by exposing it to a 1-h light pulse of 2,000 lx under constant conditions. A light pulse given at the beginning and end of the subjective night produced a phase delay and advance shifts, respectively. When pulsed around the midpoint of the subjective night, the circadian rhythm was shifted as much as 12 h in most animals or became arrhythmic in some. In the latter case, an additional light pulse restored the circadian rhythm. Some animals were unresponsive to light. The phase response curve is categorized as type 0. A large phase-shift was sometimes followed by splitting of an activity band into two components. These results are best explained by an assumption that the chipmunk circadian system is composed of two mutually coupled major oscillators, each of which is constituted by multiple oscillators. Our results suggest that light affects the oscillatory coupling not only of the major oscillators but also of constitutional oscillators.

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Diencephalon

Mayo Clinic Medical Neurosciences ◽

10.1093/med/9780190209407.003.0018 ◽

2017 ◽

pp. 627-656

Author(s):

Eduardo E. Benarroch ◽

Jeremy K. Cutsforth-Gregory ◽

Kelly D. Flemming

Keyword(s):

Cerebral Cortex ◽

Circadian Rhythm ◽

Visual System ◽

Image Formation ◽

Subcortical Structures ◽

Tentorium Cerebelli ◽

Clinical Correlates ◽

Light Reflex ◽

System A ◽

Derivatives Of

The supratentorial level includes all structures located within the skull and above the tentorium cerebelli. These structures develop from the embryonic prosencephalon and, therefore, include derivatives of the diencephalon and telencephalon. The visual system, a derivative of the diencephalon, provides input to the cerebral cortex for image formation and to subcortical structures to trigger the light reflex and entrain the circadian rhythm. This chapter discusses the anatomy, physiology, and clinical correlates of the diencephalic components of systems at the supratentorial level.

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Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

Endocrine Reviews ◽

10.1210/er.2016-1083 ◽

2016 ◽

Vol 37 (6) ◽

pp. 584-608 ◽

Cited By ~ 124

Author(s):

Gregory D. M. Potter ◽

Debra J. Skene ◽

Josephine Arendt ◽

Janet E. Cade ◽

Peter J. Grant ◽

...

Keyword(s):

Circadian Rhythm ◽

Circadian System ◽

Sleep Disruption ◽

Molecular Clocks ◽

Global Trends ◽

Artificial Lighting ◽

Dietary Choices ◽

Increased Risk ◽

Daily Cycles ◽

Pharmaceutical Interventions

Abstract Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.

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Assessment of the Effects of Nocturnal Exposure to 50-Hz Magnetic Fields on the Human Circadian System. A Comprehensive Study of Biochemical Variables

Chronobiology International ◽

10.3109/07420529909016946 ◽

1999 ◽

Vol 16 (6) ◽

pp. 789-810 ◽

Cited By ~ 18

Author(s):

Brahim Selmaoui ◽

Jacques Lambrozo ◽

Yvan Touitou

Keyword(s):

Magnetic Fields ◽

Circadian System ◽

Biochemical Variables ◽

System A ◽

Comprehensive Study

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cpmA, a Gene Involved in an Output Pathway of the Cyanobacterial Circadian System

Journal of Bacteriology ◽

10.1128/jb.181.11.3516-3524.1999 ◽

1999 ◽

Vol 181 (11) ◽

pp. 3516-3524 ◽

Cited By ~ 62

Author(s):

Mitsunori Katayama ◽

Nicholas F. Tsinoremas ◽

Takao Kondo ◽

Susan S. Golden

Keyword(s):

Vibrio Harveyi ◽

Circadian System ◽

Open Reading Frame ◽

Circadian Gene ◽

Reading Frame ◽

Circadian Phase ◽

System A ◽

Reporter Strains ◽

Pcc 7942 ◽

Low Amplitude

ABSTRACT We generated random mutations in Synechococcus sp. strain PCC 7942 to look for genes of output pathways in the cyanobacterial circadian system. A derivative of transposon Tn5 was introduced into the chromosomes of reporter strains in which cyanobacterial promoters drive the Vibrio harveyi luxAB genes and produce an oscillation of bioluminescence as a function of circadian gene expression. Among low-amplitude mutants, one mutant, tnp6, had an insertion in a 780-bp open reading frame. The tnp6 mutation produced an altered circadian phasing phenotype in the expression rhythms of psbAI::luxAB,psbAII::luxAB, andkaiA::luxAB but had no or little effect on those of psbAIII::luxAB,purF::luxAB,kaiB::luxAB,rpoD2::luxAB,ndhD::luxAB, andconII::luxAB. This suggests that the interrupted gene in tnp6, named cpmA (circadian phase modifier), is part of a circadian output pathway that regulates the expression rhythms of psbAI, psbAII, andkaiA.

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