scholarly journals A robust and self-sustained peripheral circadian oscillator reveals differences in temperature compensation properties with central brain clocks

2020 ◽  
Author(s):  
Marijke Versteven ◽  
Karla-Marlen Ernst ◽  
Ralf Stanewsky
Keyword(s):  
Temperature Compensation ◽  
Biological Rhythms ◽  
The Body ◽  
Circadian Clocks ◽  
Luciferase Reporter ◽  
Pigment Dispersing Factor ◽  
Peripheral Oscillators ◽  
Peripheral Clocks ◽  
Central Clock ◽  
Fitness And Health

AbstractCircadian clocks temporally organize physiology and behavior of organisms exposed to the daily changes of light and temperature on our planet, thereby contributing to fitness and health. Circadian clocks and the biological rhythms they control are characterized by three properties. (1) The rhythms are self-sustained in constant conditions with a period of ~ 24 hr, (2), they can be synchronized to the environmental cycles of light and temperature, and (3), they are temperature compensated, meaning they run with the same speed at different temperatures within the physiological range of the organism. Apart from the central clocks located in or near the brain, which regulate the daily activity rhythms of animals, the so-called peripheral clocks are dispersed throughout the body of insects and vertebrates. Based on the three defining properties, it has been difficult to determine if these peripheral clocks are true circadian clocks. We used a set of clock gene – luciferase reporter genes to address this question in Drosophila circadian clocks. We show that self-sustained fly peripheral oscillators over compensate temperature changes, i.e., they slow down with increasing temperature. This over-compensation is not observed in central clock neurons in the fly brain, both in intact flies and in cultured brains, suggesting that neural network properties contribute to temperature compensation. However, an important neuropeptide for synchronizing the circadian neuronal network, the Pigment Dispersing Factor (PDF), is not required for self-sustained and temperature-compensated oscillations in subsets of the central clock neurons. Our findings reveal a fundamental difference between central and peripheral clocks, which likely also applies for vertebrate clocks.

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.

scholarly journals Chronodisruption: A Poorly Recognized Feature of CKD

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 151 ◽  
Author(s):  
Sol Carriazo ◽  
Adrián M Ramos ◽  
Ana B Sanz ◽  
Maria Dolores Sanchez-Niño ◽  
Mehmet Kanbay ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Kidney Disease ◽  
Biological Rhythms ◽  
Molecular Clocks ◽  
Ckd Progression ◽  
Therapeutic Implications ◽  
Physiological Variables ◽  
Peripheral Clocks ◽  
Central Clock ◽  
The Impact

Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic.

scholarly journals Desipramine restores the alterations in circadian entrainment induced by prenatal exposure to glucocorticoids

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stefan Spulber ◽  
Mirko Conti ◽  
Frederik Elberling ◽  
Marilena Raciti ◽  
Dasiel Oscar Borroto-Escuela ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Feedback Loop ◽  
Nuclear Translocation ◽  
Clock Genes ◽  
Negative Feedback Loop ◽  
Dark Cycle ◽  
Peripheral Oscillators ◽  
Noradrenaline Reuptake ◽  
Peripheral Clocks ◽  
Central Clock

Abstract Alterations in circadian rhythms are closely linked to depression, and we have shown earlier that progressive alterations in circadian entrainment precede the onset of depression in mice exposed in utero to excess glucocorticoids. The aim of this study was to investigate whether treatment with the noradrenaline reuptake inhibitor desipramine (DMI) could restore the alterations in circadian entrainment and prevent the onset of depression-like behavior. C57Bl/6 mice were exposed to dexamethasone (DEX—synthetic glucocorticoid analog, 0.05 mg/kg/day) between gestational day 14 and delivery. Male offspring aged 6 months (mo) were treated with DMI (10 mg/kg/day in drinking water) for at least 21 days before behavioral testing. We recorded spontaneous activity using the TraffiCage™ system and found that DEX mice re-entrained faster than controls after an abrupt advance in light-dark cycle by 6 h, while DMI treatment significantly delayed re-entrainment. Next we assessed the synchronization of peripheral oscillators with the central clock (located in the suprachiasmatic nucleus—SCN), as well as the mechanisms required for entrainment. We found that photic entrainment of the SCN was apparently preserved in DEX mice, but the expression of clock genes in the hippocampus was not synchronized with the light-dark cycle. This was associated with downregulated mRNA expression for arginine vasopressin (AVP; the main molecular output entraining peripheral clocks) in the SCN, and for glucocorticoid receptor (GR; required for the negative feedback loop regulating glucocorticoid secretion) in the hippocampus. DMI treatment restored the mRNA expression of AVP in the SCN and enhanced GR-mediated signaling by upregulating GR expression and nuclear translocation in the hippocampus. Furthermore, DMI treatment at 6 mo prevented the onset of depression-like behavior and the associated alterations in neurogenesis in 12-mo-old DEX mice. Taken together, our data indicate that DMI treatment enhances GR-mediated signaling and restores the synchronization of peripheral clocks with the SCN and support the hypothesis that altered circadian entrainment is a modifiable risk factor for depression.

Modeling circadian clocks: Roles, advantages, and limitations

2011 ◽  
Vol 6 (5) ◽  
pp. 712-729 ◽  
Author(s):  
Didier Gonze
Keyword(s):  
Temperature Compensation ◽  
Molecular Level ◽  
Dynamic Properties ◽  
Biological Rhythms ◽  
Feedback Loops ◽  
Circadian Clocks ◽  
Light Pulses ◽  
Molecular Noise ◽  
Molecular Regulatory Mechanisms ◽  
Molecular Circuitry

AbstractCircadian rhythms are endogenous oscillations characterized by a period of about 24h. They constitute the biological rhythms with the longest period known to be generated at the molecular level. The abundance of genetic information and the complexity of the molecular circuitry make circadian clocks a system of choice for theoretical studies. Many mathematical models have been proposed to understand the molecular regulatory mechanisms that underly these circadian oscillations and to account for their dynamic properties (temperature compensation, entrainment by light dark cycles, phase shifts by light pulses, rhythm splitting, robustness to molecular noise, intercellular synchronization). The roles and advantages of modeling are discussed and illustrated using a variety of selected examples. This survey will lead to the proposal of an integrated view of the circadian system in which various aspects (interlocked feedback loops, inter-cellular coupling, and stochasticity) should be considered together to understand the design and the dynamics of circadian clocks. Some limitations of these models are commented and challenges for the future identified.

scholarly journals Temperature compensation and temperature sensation in the circadian clock

2015 ◽  
Vol 112 (46) ◽  
pp. E6284-E6292 ◽  
Author(s):  
Philip B. Kidd ◽  
Michael W. Young ◽  
Eric D. Siggia
Keyword(s):  
Circadian Clock ◽  
Temperature Compensation ◽  
Temperature Oscillation ◽  
Circadian Clocks ◽  
Luciferase Reporter ◽  
Alternative Theory ◽  
Temperature Dependent ◽  
Western Blots ◽  
Temperature Changes ◽  
Clock Component

All known circadian clocks have an endogenous period that is remarkably insensitive to temperature, a property known as temperature compensation, while at the same time being readily entrained by a diurnal temperature oscillation. Although temperature compensation and entrainment are defining features of circadian clocks, their mechanisms remain poorly understood. Most models presume that multiple steps in the circadian cycle are temperature-dependent, thus facilitating temperature entrainment, but then insist that the effect of changes around the cycle sums to zero to enforce temperature compensation. An alternative theory proposes that the circadian oscillator evolved from an adaptive temperature sensor: a gene circuit that responds only to temperature changes. This theory implies that temperature changes should linearly rescale the amplitudes of clock component oscillations but leave phase relationships and shapes unchanged. We show using timeless luciferase reporter measurements and Western blots against TIMELESS protein that this prediction is satisfied by the Drosophila circadian clock. We also review evidence for pathways that couple temperature to the circadian clock, and show previously unidentified evidence for coupling between the Drosophila clock and the heat-shock pathway.

scholarly journals Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 426
Author(s):  
Giuseppe Bellastella ◽  
Maria Ida Maiorino ◽  
Lorenzo Scappaticcio ◽  
Annamaria De Bellis ◽  
Silvia Mercadante ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Biological Rhythms ◽  
Cellular Level ◽  
Scientific Discipline ◽  
Biological Phenomena ◽  
Pituitary Thyroid Axis ◽  
Circadian Organization ◽  
Thyroid Axis ◽  
Central Clock ◽  
Thyroid Dysfunctions

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the control of a central clock, and the hormones of the pituitary–thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer.

scholarly journals A circadian clock in a nonphotosynthetic prokaryote

2021 ◽  
Vol 7 (2) ◽  
pp. eabe2086
Author(s):  
Zheng Eelderink-Chen ◽  
Jasper Bosman ◽  
Francesca Sartor ◽  
Antony N. Dodd ◽  
Ákos T. Kovács ◽  
...  
Keyword(s):  
Temperature Compensation ◽  
Temporal Structure ◽  
Bacterial Biofilm ◽  
Circadian Clocks ◽  
Industrial Processes ◽  
Free Living ◽  
Considerable Potential ◽  
Free Running ◽  
Free Running Period ◽  
Constant Dark

Circadian clocks create a 24-hour temporal structure, which allows organisms to occupy a niche formed by time rather than space. They are pervasive throughout nature, yet they remain unexpectedly unexplored and uncharacterized in nonphotosynthetic bacteria. Here, we identify in Bacillus subtilis circadian rhythms sharing the canonical properties of circadian clocks: free-running period, entrainment, and temperature compensation. We show that gene expression in B. subtilis can be synchronized in 24-hour light or temperature cycles and exhibit phase-specific characteristics of entrainment. Upon release to constant dark and temperature conditions, bacterial biofilm populations have temperature-compensated free-running oscillations with a period close to 24 hours. Our work opens the field of circadian clocks in the free-living, nonphotosynthetic prokaryotes, bringing considerable potential for impact upon biomedicine, ecology, and industrial processes.

scholarly journals Genetic interactions between clock mutations in Neurospora crassa : can they help us to understand complexity?

2001 ◽  
Vol 356 (1415) ◽  
pp. 1717-1724 ◽  
Author(s):  
Louis W. Morgan ◽  
Jerry F. Feldman ◽  
Deborah Bell-Pedersen
Keyword(s):  
Coupled Oscillators ◽  
Temperature Compensation ◽  
White Collar ◽  
Circadian System ◽  
Genetic Interactions ◽  
Circadian Clocks ◽  
Metabolic Effects ◽  
Clock Model ◽  
Number Of Genes ◽  
Single Oscillator

Recent work on circadian clocks in Neurospora has primarily focused on the frequency ( frq ) and white–collar ( wc ) loci. However, a number of other genes are known that affect either the period or temperature compensation of the rhythm. These include the period (no relationship to the period gene of Drosophila ) genes and a number of genes that affect cellular metabolism. How these other loci fit into the circadian system is not known, and metabolic effects on the clock are typically not considered in single–oscillator models. Recent evidence has pointed to multiple oscillators in Neurospora , at least one of which is predicted to incorporate metabolic processes. Here, the Neurospora clock–affecting mutations will be reviewed and their genetic interactions discussed in the context of a more complex clock model involving two coupled oscillators: a FRQ/WC–based oscillator and a ‘ frq –less’ oscillator that may involve metabolic components.

THE ROLE OF CIRCADIAN REGULATION OF GHRELIN LEVELS IN PARKINSON’S DISEASE (LITERATURE REVIEW)

2021 ◽  
Vol 74 (7) ◽  
pp. 1750-1753
Author(s):  
Kateryna A. Tarianyk ◽  
Nataliya V. Lytvynenko ◽  
Anastasiia D. Shkodina ◽  
Igor P. Kaidashev
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clock Genes ◽  
Biological Rhythms ◽  
Circadian Regulation ◽  
Diurnal Changes ◽  
Dopaminergic Therapy ◽  
Peripheral Oscillators ◽  
Genes Expression

The paper is aimed at the analysis of the role of the circadian regulation of ghrelin levels in patients with Parkinson’s disease. Based on the literature data, patients with Parkinson’s disease have clinical fluctuations in the symptoms of the disease, manifested by the diurnal changes in motor activity, autonomic functions, sleep-wake cycle, visual function, and the efficacy of dopaminergic therapy. Biological rhythms are controlled by central and peripheral oscillators which links with dopaminergic neurotransmission – core of the pathogenesis of Parkinson`s disease. Circadian system is altered in Parkinson`s disease due to that ghrelin fluctuations may be changed. Ghrelin is potential food-entrainable oscillator because it is linked with clock genes expression. In Parkinson`s disease this hormone may induce eating behavior changing and as a result metabolic disorder. The “hunger hormone” ghrelin can be a biomarker of the Parkinson’s disease, and the study of its role in the pathogenesis, as well as its dependence on the period of the day, intake of levodopa medications to improve the effectiveness of treatment is promising.

scholarly journals An ultradian feeding schedule in rats affects metabolic gene expression in liver, brown adipose tissue and skeletal muscle with only mild effects on circadian clocks

2018 ◽  
Author(s):  
Paul de Goede ◽  
Satish Sen ◽  
Yan Su ◽  
Ewout Foppen ◽  
Vincet-Joseph Poirel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Feeding Behavior ◽  
Circadian Clocks ◽  
Daily Rhythm ◽  
Feeding Schedule ◽  
Metabolic Gene Expression ◽  
Brown Adipose ◽  
Peripheral Clocks ◽  
Master Clock

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6-meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock but did have mild effects on peripheral clocks. By contrast, genes involved in glucose and lipid metabolism showed differential expression. Concluding, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.

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