Molecular Biology and Physiology of Circadian Clocks

2019 ◽  
Author(s):  
Ruifeng Cao
Keyword(s):  
Circadian Rhythms ◽  
Circadian System ◽  
Feedback Loops ◽  
The Body ◽  
Endogenous Rhythms ◽  
Peripheral Oscillators ◽  
Physiological Processes ◽  
And Behavior ◽  
Photic Input ◽  
Master Clock

Circadian rhythm is the approximately 24-hour rhythmicity that regulates physiology and behavior in a variety of organisms. The mammalian circadian system is organized in a hierarchical manner. Molecular circadian oscillations driven by genetic feedback loops are found in individual cells, whereas circadian rhythms in different systems of the body are orchestrated by the master clock in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. SCN receives photic input from retina and synchronizes endogenous rhythms with the external light/dark cycles. SCN regulates circadian rhythms in the peripheral oscillators via neural and humoral signals, which account for daily fluctuations of the physiological processes in these organs. Disruption of circadian rhythms can cause health problems and circadian dysfunction has been linked to many human diseases.

scholarly journals The Kidney Clock Contributes to Timekeeping by the Master Circadian Clock

2019 ◽  
Vol 20 (11) ◽  
pp. 2765 ◽  
Author(s):  
Jihwan Myung ◽  
Mei-Yi Wu ◽  
Chun-Ya Lee ◽  
Amalia Ridla Rahim ◽  
Vuong Hung Truong ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Sleep Disturbances ◽  
The Body ◽  
Circadian Clocks ◽  
Whole Body ◽  
The Hierarchical Structure ◽  
Body Level ◽  
The Brain ◽  
Master Clock

The kidney harbors one of the strongest circadian clocks in the body. Kidney failure has long been known to cause circadian sleep disturbances. Using an adenine-induced model of chronic kidney disease (CKD) in mice, we probe the possibility that such sleep disturbances originate from aberrant circadian rhythms in kidney. Under the CKD condition, mice developed unstable behavioral circadian rhythms. When observed in isolation in vitro, the pacing of the master clock, the suprachiasmatic nucleus (SCN), remained uncompromised, while the kidney clock became a less robust circadian oscillator with a longer period. We find this analogous to the silencing of a strong slave clock in the brain, the choroid plexus, which alters the pacing of the SCN. We propose that the kidney also contributes to overall circadian timekeeping at the whole-body level, through bottom-up feedback in the hierarchical structure of the mammalian circadian clocks.

scholarly journals Neurochemical mechanisms and pharmacology of ghrelins

2020 ◽  
Vol 18 (1) ◽  
pp. 5-22
Author(s):  
Petr D. Shabanov ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov ◽  
Nikanor V. Lavrov ◽  
Vitalii I. Morozov
Keyword(s):  
The Body ◽  
Molecular Forms ◽  
Pharmacological Agents ◽  
Ghrelin Receptor ◽  
Physiological Processes ◽  
History Of ◽  
Ghrelin Receptors ◽  
Neurophysiological Mechanisms ◽  
And Behavior ◽  
The Brain

The purpose of the review was to analyze the neurochemical and neurophysiological mechanisms of the ghrelin system and the role of ghrelin in body functions and behavior. The focus is on the participation of ghrelin in the mechanisms of reinforcement and the formation of addictive behavior. At the beginning of the review a history of the first works on the field of ghrelin and its receptor was described. Then, genetic control, molecular precursor of ghrelin, molecular forms of ghrelin and ghrelin receptor were represented. In particular, the distribution of the ghrelin receptor, ghrelin-producing cells in the brain and its participation in various physiological functions of the body were shown. The hypothalamic functions of ghrelin were discussed: energy balance, regulation of glucose metabolism, stimulation of eating behavior, regulation of hypophys-pituitary axis (HPA) system. The connection of ghrelin with the brain CRH system was demonstrated. In particular, activation of HPA was described as a possible mechanism through which ghrelin regulates a number of physiological processes. Extrahypothalamic action of ghrelin was shown on the basis of the mechanisms of reinforcement and addiction. On the basis of their own data and literary, it was concluded that action of alcohol and psychoactive drugs are reduced after the ghrelin receptors blockade. In particular, it has been demonstrated that alcoholization of mothers affects the activity of the ghrelin system during the prenatal and early postnatal periods of development in the offspring of rats. It was shown the participation of ghrelin in memory and learning. The further perspective of the study and practical application of ghrelin-based pharmacological agents was analyzed.

scholarly journals Minireview: The Neuroendocrinology of the Suprachiasmatic Nucleus as a Conductor of Body Time in Mammals

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5640-5647 ◽  
Author(s):  
Ilia N. Karatsoreos ◽  
Rae Silver
Keyword(s):  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Hormone Secretion ◽  
Gonadal Hormone ◽  
Multiple Levels ◽  
And Behavior ◽  
Circadian Behavior ◽  
The Brain ◽  
Indirect Route ◽  
Photic Input

Circadian rhythms in physiology and behavior are regulated by a master clock resident in the suprachiasmatic nucleus (SCN) of the hypothalamus, and dysfunctions in the circadian system can lead to serious health effects. This paper reviews the organization of the SCN as the brain clock, how it regulates gonadal hormone secretion, and how androgens modulate aspects of circadian behavior known to be regulated by the SCN. We show that androgen receptors are restricted to a core SCN region that receives photic input as well as afferents from arousal systems in the brain. We suggest that androgens modulate circadian behavior directly via actions on the SCN and that both androgens and estrogens modulate circadian rhythms through an indirect route, by affecting overall activity and arousal levels. Thus, this system has multiple levels of regulation; the SCN regulates circadian rhythms in gonadal hormone secretion, and hormones feed back to influence SCN functions.

scholarly journals Does a Red House Affect Rhythms in Mice with a Corrupted Circadian System?

2021 ◽  
Vol 22 (5) ◽  
pp. 2288
Author(s):  
Menekse Öztürk ◽  
Marc Ingenwerth ◽  
Martin Sager ◽  
Charlotte von Gall ◽  
Amira A. H. Ali
Keyword(s):  
Circadian Rhythms ◽  
Neuronal Activity ◽  
Clock Genes ◽  
Plasma Corticosterone ◽  
Cellular Level ◽  
Circadian System ◽  
Targeted Deletion ◽  
Long Wavelength ◽  
And Behavior ◽  
Time Information

The circadian rhythms of body functions in mammals are controlled by the circadian system. The suprachiasmatic nucleus (SCN) in the hypothalamus orchestrates subordinate oscillators. Time information is conveyed from the retina to the SCN to coordinate an organism’s physiology and behavior with the light/dark cycle. At the cellular level, molecular clockwork composed of interlocked transcriptional/translational feedback loops of clock genes drives rhythmic gene expression. Mice with targeted deletion of the essential clock gene Bmal1 (Bmal1−/−) have an impaired light input pathway into the circadian system and show a loss of circadian rhythms. The red house (RH) is an animal welfare measure widely used for rodents as a hiding place. Red plastic provides light at a low irradiance and long wavelength—conditions which affect the circadian system. It is not known yet whether the RH affects rhythmic behavior in mice with a corrupted circadian system. Here, we analyzed whether the RH affects spontaneous locomotor activity in Bmal1−/− mice under standard laboratory light conditions. In addition, mPER1- and p-ERK-immunoreactions, as markers for rhythmic SCN neuronal activity, and day/night plasma corticosterone levels were evaluated. Our findings indicate that application of the RH to Bmal1−/− abolishes rhythmic locomotor behavior and dampens rhythmic SCN neuronal activity. However, RH had no effect on the day/night difference in corticosterone levels.

scholarly journals Impact of nutrients on circadian rhythmicity

2015 ◽  
Vol 308 (5) ◽  
pp. R337-R350 ◽  
Author(s):  
Johanneke E. Oosterman ◽  
Andries Kalsbeek ◽  
Susanne E. la Fleur ◽  
Denise D. Belsham
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
The Body ◽  
Circadian Rhythmicity ◽  
Energy Status ◽  
Peripheral Oscillators ◽  
Peripheral Clocks ◽  
Central Pacemaker ◽  
Almost All ◽  
The Impact

The suprachiasmatic nucleus (SCN) in the mammalian hypothalamus functions as an endogenous pacemaker that generates and maintains circadian rhythms throughout the body. Next to this central clock, peripheral oscillators exist in almost all mammalian tissues. Whereas the SCN is mainly entrained to the environment by light, peripheral clocks are entrained by various factors, of which feeding/fasting is the most important. Desynchronization between the central and peripheral clocks by, for instance, altered timing of food intake can lead to uncoupling of peripheral clocks from the central pacemaker and is, in humans, related to the development of metabolic disorders, including obesity and Type 2 diabetes. Diets high in fat or sugar have been shown to alter circadian clock function. This review discusses the recent findings concerning the influence of nutrients, in particular fatty acids and glucose, on behavioral and molecular circadian rhythms and will summarize critical studies describing putative mechanisms by which these nutrients are able to alter normal circadian rhythmicity, in the SCN, in non-SCN brain areas, as well as in peripheral organs. As the effects of fat and sugar on the clock could be through alterations in energy status, the role of specific nutrient sensors will be outlined, as well as the molecular studies linking these components to metabolism. Understanding the impact of specific macronutrients on the circadian clock will allow for guidance toward the composition and timing of meals optimal for physiological health, as well as putative therapeutic targets to regulate the molecular clock.

Free-Running Human Circadian Rhythms in Svalbard

1979 ◽  
Vol 34 (5-6) ◽  
pp. 470-473 ◽  
Author(s):  
A. Johnsson ◽  
W. Engelmann ◽  
W. Klemke ◽  
Aud Tveito Ekse
Keyword(s):  
Body Temperature ◽  
Circadian Rhythms ◽  
Continuous Light ◽  
Circadian System ◽  
The Body ◽  
The Arctic ◽  
Light Conditions ◽  
Temperature Recording ◽  
Rest Time ◽  
Free Running

Abstract The body temperature, activity-rest time, electrolytes of urine samples and mood was measured in two persons during a 19 day period under continuous light conditions in the arctic (vicinity of Ny Ålesund, Svalbard-Spitsbergen). For temperature recording a new thermoprobe and a portable printer was used. Possible week Zeitgeber of the 24 hour day did not synchronize the circadian system, since circadian rhythms of about 26 hours were found. These results open up the pos­ sibility to study effects of drugs on the circadian system of humans under Svalbard conditions.

scholarly journals Reversible modulation of circadian time with chronophotopharmacology

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dušan Kolarski ◽  
Carla Miró-Vinyals ◽  
Akiko Sugiyama ◽  
Ashutosh Srivastava ◽  
Daisuke Ono ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Small Molecules ◽  
Molecular Design ◽  
State Of The Art ◽  
The Body ◽  
Casein Kinase I ◽  
Physiological Processes ◽  
Circadian Time ◽  
Clock Mechanism

AbstractThe circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIα and CKIδ isoforms, while upon irradiation it becomes more selective towards CKIδ, revealing the higher importance of CKIδ in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology.

scholarly journals Central and peripheral oscillators in mammals: A guided tour through a network of clocks

2004 ◽  
Vol 26 (1) ◽  
pp. 23-25
Author(s):  
Fabienne Guillaumond ◽  
Nicolas Cermakian
Keyword(s):  
Circadian Rhythms ◽  
Circadian System ◽  
Oscillator System ◽  
Peripheral Oscillators ◽  
Circadian Oscillators ◽  
Guided Tour ◽  
Different Tissues

For decades, the circadian system of animals was viewed as a single or a few centralized structures driving all overt physiological circadian rhythms. Recent data have questioned this view and have revealed a much more complex and dynamic picture. We now know that circadian oscillators are also present in many different tissues and constitute part of a hierarchical circadian system. In this article, we describe this multi-oscillator system that constitutes the basis for the variety of physiological rhythms.

scholarly journals Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Depression

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Roberto Salgado-Delgado ◽  
Araceli Tapia Osorio ◽  
Nadia Saderi ◽  
Carolina Escobar
Keyword(s):  
Circadian Rhythms ◽  
Biological Clock ◽  
Therapeutic Strategies ◽  
Circadian System ◽  
Metabolic Functions ◽  
Lighting Conditions ◽  
Wide Range ◽  
Close Relationship ◽  
And Behavior ◽  
Depressive States

Circadian factors might play a crucial role in the etiology of depression. It has been demonstrated that the disruption of circadian rhythms by lighting conditions and lifestyle predisposes individuals to a wide range of mood disorders, including impulsivity, mania and depression. Also, associated with depression, there is the impairment of circadian rhythmicity of behavioral, endocrine, and metabolic functions. Inspite of this close relationship between both processes, the complex relationship between the biological clock and the incidence of depressive symptoms is far from being understood. The efficiency and the timing of treatments based on chronotherapy (e.g., light treatment, sleep deprivation, and scheduled medication) indicate that the circadian system is an essential target in the therapy of depression. The aim of the present review is to analyze the biological and clinical data that link depression with the disruption of circadian rhythms, emphasizing the contribution of circadian desynchrony. Therefore, we examine the conditions that may lead to circadian disruption of physiology and behavior as described in depressive states, and, according to this approach, we discuss therapeutic strategies aimed at treating the circadian system and depression.

scholarly journals Phosphorylation and Circadian Molecular Timing

2020 ◽  
Vol 11 ◽  
Author(s):  
Andrea Brenna ◽  
Urs Albrecht
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Environmental Changes ◽  
Circadian System ◽  
Post Translational Modifications ◽  
Physiological Processes ◽  
Clock Proteins ◽  
Protein Components ◽  
Response To Environmental Change ◽  
External Stimuli

Endogenous circadian rhythms are biological processes generated by an internal body clock. They are self-sustaining, and they govern biochemical and physiological processes. However, circadian rhythms are influenced by many external stimuli to reprogram the phase in response to environmental change. Through their adaptability to environmental changes, they synchronize physiological responses to environmental challenges that occur within a sidereal day. The precision of this circadian system is assured by many post-translational modifications (PTMs) that occur on the protein components of the circadian clock mechanism. The most ancient example of circadian rhythmicity driven by phosphorylation of clock proteins was observed in cyanobacteria. The influence of phosphorylation on the circadian system is observed through different kingdoms, from plants to humans. Here, we discuss how phosphorylation modulates the mammalian circadian clock, and we give a detailed overview of the most critical discoveries in the field.

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