Minimally Invasive Ways of Determining Circadian Rhythms in Humans

Physiology ◽  
2021 ◽  
Vol 36 (1) ◽  
pp. 7-20 ◽  
Author(s):  
Sandra Crnko ◽  
Hilde Schutte ◽  
Pieter A. Doevendans ◽  
Joost P. G. Sluijter ◽  
Linda W. van Laake
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Minimally Invasive ◽  
Circadian Clock ◽  
Critical Role ◽  
Health And Disease

Circadian rhythm exerts a critical role in mammalian health and disease. A malfunctioning circadian clock can be a consequence, as well as the cause of several pathophysiologies. Clinical therapies and research may also be influenced by the clock. Since the most suitable manner of revealing this rhythm in humans is not yet established, we discuss existing methods and seek to determine the most feasible ones.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals BMAL1 but not CLOCK is associated with monochromatic green light-induced circadian rhythm of melatonin in chick pinealocytes

2019 ◽  
Vol 8 (1) ◽  
pp. 57-68 ◽  
Author(s):  
Shuhui Ma ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong ◽  
Yaoxing Chen
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Clock Genes ◽  
Critical Role ◽  
Green Light ◽  
Circadian Oscillator ◽  
Melatonin Secretion ◽  
Expression Levels

The avian pineal gland, an independent circadian oscillator, receives external photic cues and translates them for the rhythmical synthesis of melatonin. Our previous study found that monochromatic green light could increase the secretion of melatonin and expression of CLOCK and BMAL1 in chick pinealocytes. This study further investigated the role of BMAL1 and CLOCK in monochromatic green light-induced melatonin secretion in chick pinealocytes using siRNAs interference and overexpression techniques. The results showed that si-BMAL1 destroyed the circadian rhythms of AANAT and melatonin, along with the disruption of the expression of all the seven clock genes, except CRY1. Furthermore, overexpression of BMAL1 also disturbed the circadian rhythms of AANAT and melatonin, in addition to causing arrhythmic expression of BMAL1 and CRY1/2, but had no effect on the circadian rhythms of CLOCK, BMAL2 and PER2/3. The knockdown or overexpression of CLOCK had no impact on the circadian rhythms of AANAT, melatonin, BMAL1 and PER2, but it significantly deregulated the circadian rhythms of CLOCK, BMAL2, CRY1/2 and PER3. These results suggested that BMAL1 rather than CLOCK plays a critical role in the regulation of monochromatic green light-induced melatonin rhythm synthesis in chicken pinealocytes. Moreover, both knockdown and overexpression of BMAL1 could change the expression levels of CRY2, it indicated CRY2 may be involved in the BMAL1 pathway by modulating the circadian rhythms of AANAT and melatonin.

scholarly journals Circadian rhythm and neurodegenerative disorders

2020 ◽  
Vol 6 (2) ◽  
pp. 71-80
Author(s):  
Michelle Werdann ◽  
Yong Zhang
Keyword(s):  
Circadian Rhythm ◽  
Early Intervention ◽  
Circadian Rhythms ◽  
Neurodegenerative Diseases ◽  
Circadian Clock ◽  
Neurodegenerative Disorders ◽  
Circadian Clocks ◽  
Daily Rhythms ◽  
Animal Physiology ◽  
And Behavior

The circadian clock controls daily rhythms in animal physiology, metabolism, and behavior, such as the sleep‐wake cycle. Disruption of circadian rhythms has been revealed in many diseases including neurodegenerative disorders. Interestingly, patients with many neurodegenerative diseases often show problems with circadian clocks even years before other symptoms develop. Here we review the recent studies identifying the association between circadian rhythms and several major neurodegenerative disorders. Early intervention of circadian rhythms may benefit the treatment of neurodegeneration.

scholarly journals Simulated Space Environmental Factors of Weightlessness, Noise and Low Air Pressure Differentially Affect the Circadian Rhythm and Gut Microbiome

2021 ◽  
Author(s):  
Huan Ma ◽  
Xihui Gan ◽  
Jianwei Zhao ◽  
Yin Zhang ◽  
Silin Li ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Community Structure ◽  
Circadian Rhythms ◽  
Environmental Factors ◽  
Circadian Clock ◽  
Gut Microbiome ◽  
Atmospheric Pressure ◽  
Clock Genes ◽  
Low Atmospheric Pressure ◽  
Space Capsule

Abstract Backgroundhe circadian clock extensively regulates physiology and behavior. In space, the astronauts encounter many environmental factors that are dramatically different from those on earth, however, the effects of these factors on circadian rhythms and the mechanisms remain largely unknown. The present study aimed to investigate the changes in the mouse circadian rhythm and gut microbiome under simulated space capsule conditions, including microgravity, noise and low atmospheric pressure.ResultsNoise and low atmospheric pressure were loaded in the capsule while the conditions in the animal room remained constant. The mice in the capsule showed disturbed locomotor rhythms and faster adaptation to a 6-h phase advance. RNA sequencing of hypothalamus samples revealed that microgravity simulated by hind limb unloading (HU) and exposure to noise and low atmospheric pressure led to decreases in the quantities of differentially expressed genes (DEGs), including circadian clock genes. Changes in the rhythmicity of genes implicated in pathways of cardiovascular deconditioning and more concentrated circadian phases were found under HU or noise and low atmospheric pressure. Furthermore, 16S rRNA sequencing revealed dysbiosis in the gut microbiome, and noise and low atmospheric pressure may repress the temporal discrepancy in the microbiome community structure induced by microgravity. Changes in diel oscillation were observed in a number of gut bacteria with critical physiological consequences in metabolism and immunodefense.ConclusionsOur data demonstrate that in addition to microgravity, exposure to noise and low atmospheric pressure affect the robustness of circadian rhythms and the community structure of the gut microbiome, and these factors may interfere with each other in their adaptation to respective conditions. These findings are important to further our understanding of the alteration of circadian rhythms in the space complex environment.

scholarly journals Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer’s disease and longevity in an Italian population

GeroScience ◽  
2021 ◽  
Author(s):  
Maria Giulia Bacalini ◽  
Flavia Palombo ◽  
Paolo Garagnani ◽  
Cristina Giuliani ◽  
Claudio Fiorini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Successful Aging ◽  
Clock Genes ◽  
Association Studies ◽  
Italian Population ◽  
Age Related

AbstractMany physiological processes in the human body follow a 24-h circadian rhythm controlled by the circadian clock system. Light, sensed by retina, is the predominant “zeitgeber” able to synchronize the circadian rhythms to the light-dark cycles. Circadian rhythm dysfunction and sleep disorders have been associated with aging and neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In the present study, we aimed at investigating the genetic variability of clock genes in AD patients compared to healthy controls from Italy. We also included a group of Italian centenarians, considered as super-controls in association studies given their extreme phenotype of successful aging. We analyzed the exon sequences of eighty-four genes related to circadian rhythms, and the most significant variants identified in this first discovery phase were further assessed in a larger independent cohort of AD patients by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The results identified a significant association between the rs3027178 polymorphism in the PER1 circadian gene with AD, the G allele being protective for AD. Interestingly, rs3027178 showed similar genotypic frequencies among AD patients and centenarians. These results collectively underline the relevance of circadian dysfunction in the predisposition to AD and contribute to the discussion on the role of the relationship between the genetics of age-related diseases and of longevity.

scholarly journals Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

2016 ◽  
Vol 2 (9) ◽  
pp. e1600960 ◽  
Author(s):  
Daisuke Ono ◽  
Sato Honma ◽  
Ken-ichi Honma
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Clock Gene ◽  
Critical Role ◽  
Tissue Level ◽  
Postnatal Period ◽  
Gene Products ◽  
Adult Mice ◽  
Multiple Clusters ◽  
Deficient Mice

The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period.

Abstract 430: Circadian Control of Heart Rate

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Alicia D’souza ◽  
Sven Wegner ◽  
Anne Berit Johnsen ◽  
Eleanor Gill ◽  
Charlotte Cox ◽  
...  
Keyword(s):  
Heart Rate ◽  
Transcription Factors ◽  
Circadian Rhythm ◽  
Ion Channels ◽  
Circadian Rhythms ◽  
Ion Channel ◽  
Circadian Clock ◽  
Alternative Hypothesis ◽  
Cardiac Pacemaker ◽  
Upstream Region

Background: Bradyarrhythmias occur more frequently at night. On the basis of heart rate variability this is attributed to high vagal tone. Here we tested the alternative hypothesis that an intrinsic circadian clock-driven remodelling of pacemaking ion channels underlies fluctuations in heart rate (HR). Methods and results: The occurrence of a circadian rhythm in HR was tested by placing nocturnal C57BL6/J mice under a strict 12/12h light-dark cycle and telemetry-based ECG intervals measured every 2 h for 48 h. Under these conditions, the R-R interval was rhythmic (n=10). To test whether this is caused by circadian rhythms in the expression of ion channels controlling HR, sinus node (SAN) biopsies were collected at time points corresponding to the minima (ZT0, subjective day) and maxima (ZT12, subjective night) of HR, as determined by ECG recordings. Real-time PCR normalised to 28s demonstrated an elevated expression of the key pacemaking ion channel HCN4 that carries the pacemaker current I f and genes encoding the Ca 2+ -handling proteins SERCA2a and RYR2 at ZT12 ( P <0.05, n=10). Presence of clock machinery (essential transcription factors involved in setting intrinsic circadian rhythms) as potential regulators of ion channel oscillation were investigated in the SAN of mPer1 Luc mice which carry the 5’ upstream region of the mPer1 gene (a key core clock component) fused to a luciferase gene. mPer1-luc bioluminescence was recorded in the isolated SAN using a light-tight photomultiplier tube assembly to reveal a circadian rhythm with a periodicity of 24 h (n=3). Disruption of the molecular clock by global knockout of core clock components Cry1 and Cry2 abrogated the circadian cycling of mPer1-luc in the SN of Cry1 -/- /Cry2 -/- double knockout mice (n=3). Examination of 10[[Unable to Display Character: &#8201;]]kb of the Hcn4 promoter revealed a conserved consensus binding site for CLOCK and its heterodimer BMAL1, other essential transcription factors involved in setting intrinsic circadian rhythms. Conclusions: This is the first demonstration of a peripheral circadian clock in the cardiac pacemaker and circadian oscillations in key pacemaker mechanisms. Data reveal a novel regulator of SN function and the occurrence of bradyarrythmias at night.

scholarly journals Aging Alters Circadian Rhythms in the Mouse Eye

2018 ◽  
Vol 33 (4) ◽  
pp. 441-445 ◽  
Author(s):  
Kenkichi Baba ◽  
Gianluca Tosini
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Circadian System ◽  
Ocular Tissues ◽  
Effects Of Aging ◽  
Ocular System ◽  
The Brain

The eye contains a circadian system that acts independently from the master circadian clock located in the brain. This circadian system regulates important physiological functions within the eye. Emerging experimental evidence also indicates that disruption of the ocular circadian clock, or its outputs, negatively affects the overall health of the eye. Although previous studies have investigated the effect of aging on the regulation of circadian rhythms, no study has investigated the effects of aging on the circadian rhythm in the ocular system. The aim of the present study was to investigate how aging affects the circadian rhythm of PER2::LUC bioluminescence in the retina, retinal pigment epithelium (RPE), and cornea. Our data suggest that among the 3 different ocular tissues investigated, the retina appears to be the most affected by aging whereas the RPE and cornea are less affected by aging. Our data, along with studies of other organs and tissues, suggest that reduction in the amplitude of rhythms is probably the most severe effect of aging on the circadian clock.

scholarly journals Distinct control of PERIOD2 degradation and circadian rhythms by the oncoprotein MDM2

2018 ◽  
Author(s):  
JingJing Liu ◽  
Xianlin Zou ◽  
Tetsuya Gotoh ◽  
Anne M. Brown ◽  
Liang Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Biological Systems ◽  
Period Length ◽  
Circadian Period ◽  
Functional Elements ◽  
Post Translational Modifications ◽  
Independent Mechanism

ABSTRACTThe circadian clock relies on post-translational modifications to set the timing for degradation of core regulatory components and, thus, sets clock progression. Ubiquitin-modifying enzymes targeting clock components for degradation are known to mostly recognize phosphorylated substrates. A case in point is the circadian factor PERIOD 2 (PER2) whose phospho-specific turnover involves its recognition by β-transducin repeat containing proteins (β-TrCPs). Yet, the existence of this unique mode of regulation of PER2’s stability falls short of explaining persistent oscillatory phenotypes reported in biological systems lacking functional elements of the phospho-dependent PER2 degradation machinery.In this study, we challenge the phosphorylation-centric view that PER2 degradation enhances circadian rhythm robustness by i) identifying the PER2:MDM2 endogenous complex, ii) establishing PER2 as a previously uncharacterized substrate for MDM2, iii) revealing an alternative phosphorylation-independent mechanism for PER2 ubiquitin-mediated degradation, iv) pinpointing residues for ubiquitin modification, and v) establishing the importance of MDM2-mediated PER2 turnover for defining the circadian period length. Our results not only expand MDM2’s suite of specific substrates beyond the cell cycle to include circadian components but also uncover novel regulatory players that likely impact our view of how other mechanisms crosstalk and modulate the clock itself.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

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