scholarly journals Epigenetic Regulation of Circadian Clocks and Its Involvement in Drug Addiction

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1263
Author(s):  
Lamis Saad ◽  
Jean Zwiller ◽  
Andries Kalsbeek ◽  
Patrick Anglard
Keyword(s):  
Circadian Clock ◽  
Drug Addiction ◽  
Epigenetic Regulation ◽  
Molecular Mechanisms ◽  
Feedback System ◽  
Circadian Clocks ◽  
Shift Workers ◽  
Timing System ◽  
Small Regulatory Rnas ◽  
Circadian Timing System

Based on studies describing an increased prevalence of addictive behaviours in several rare sleep disorders and shift workers, a relationship between circadian rhythms and addiction has been hinted for more than a decade. Although circadian rhythm alterations and molecular mechanisms associated with neuropsychiatric conditions are an area of active investigation, success is limited so far, and further investigations are required. Thus, even though compelling evidence connects the circadian clock to addictive behaviour and vice-versa, yet the functional mechanism behind this interaction remains largely unknown. At the molecular level, multiple mechanisms have been proposed to link the circadian timing system to addiction. The molecular mechanism of the circadian clock consists of a transcriptional/translational feedback system, with several regulatory loops, that are also intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape shows profound changes in the addictive brain, with significant alterations in histone modification, DNA methylation, and small regulatory RNAs. The combination of these two observations raises the possibility that epigenetic regulation is a common plot linking the circadian clocks with addiction, though very little evidence has been reported to date. This review provides an elaborate overview of the circadian system and its involvement in addiction, and we hypothesise a possible connection at the epigenetic level that could further link them. Therefore, we think this review may further improve our understanding of the etiology or/and pathology of psychiatric disorders related to drug addiction.

scholarly journals Photoperiodic Requirements for Induction and Maintenance of Rhythm Bifurcation and Extraordinary Entrainment in Male Mice

2019 ◽  
Vol 1 (3) ◽  
pp. 290-305 ◽  
Author(s):  
Jonathan Sun ◽  
Deborah A. M. Joye ◽  
Andrew H. Farkas ◽  
Michael R. Gorman
Keyword(s):  
Male Mice ◽  
Shift Workers ◽  
Circadian Timing ◽  
Non Invasive ◽  
Circadian Control ◽  
Timing System ◽  
Circadian Timing System ◽  
Activity Cycles ◽  
Rest Activity

Exposure of mice to a 24 h light:dark:light:dark (LDLD) cycle with dimly illuminated nights induces the circadian timing system to program two intervals of activity and two intervals of rest per 24 h cycle and subsequently allows entrainment to a variety of extraordinary light regimens including 30 h LDLD cycles. Little is known about critical lighting requirements to induce and maintain this non-standard entrainment pattern, termed “bifurcation,” and to enhance the range of apparent entrainment. The current study determined the necessary duration of the photophase for animals to bifurcate and assessed whether requirements for maintenance differed from those for induction. An objective index of bifurcated entrainment varied with length of the photophase over 4–10 h durations, with highest values at 8 h. To assess photic requirements for the maintenance of bifurcation, mice from each group were subsequently exposed to the LDLD cycle with 4 h photophases. While insufficient to induce bifurcation, this photoperiod maintained bifurcation in mice transferred from inductive LDLD cycles. Entrainment to 30 h LDLD cycles also varied with photoperiod duration. These studies characterize non-invasive tools that reveal latent flexibility in the circadian control of rest/activity cycles with important translational potential for addressing needs of human shift-workers.

scholarly journals Independence of Circadian Timing from Cell Division in Cyanobacteria

2001 ◽  
Vol 183 (8) ◽  
pp. 2439-2444 ◽  
Author(s):  
Tetsuya Mori ◽  
Carl Hirschie Johnson
Keyword(s):  
Gene Expression ◽  
Cell Division ◽  
Circadian Clock ◽  
Clock Gene ◽  
Circadian Clock Gene ◽  
Circadian Timing ◽  
Wide Range ◽  
Timing System ◽  
Circadian Timing System ◽  
Cell Division Timing

ABSTRACT In the cyanobacterium Synechococcus elongatus, cell division is regulated by a circadian clock. Deletion of the circadian clock gene, kaiC, abolishes rhythms of gene expression and cell division timing. Overexpression of the ftsZ gene halted cell division but not growth, causing cells to grow as filaments without dividing. The nondividing filamentous cells still exhibited robust circadian rhythms of gene expression. This result indicates that the circadian timing system is independent of rhythmic cell division and, together with other results, suggests that the cyanobacterial circadian system is stable and well sustained under a wide range of intracellular conditions.

Evolution and Design of Invertebrate Circadian Clocks

2017 ◽  
pp. 594-614 ◽  
Author(s):  
Vu H. Lam ◽  
Joanna C. Chiu
Keyword(s):  
Circadian Clock ◽  
Neuronal Network ◽  
External Environment ◽  
Circadian Clocks ◽  
Daily Activities ◽  
Endogenous Timing ◽  
Diverse Group ◽  
Temporal Cues ◽  
Wide Range ◽  
Timing System

Invertebrates are an incredibly diverse group of animals that come in all shapes and sizes, and live in a wide range of habitats. In order for all these organisms to perform optimally, they need to organize their daily activities and physiology around the perpetuating day-night cycles that exist on Earth. The circadian clock is the endogenous timing system that enables organisms to anticipate daily environmental cycles and governs these roughly 24-hour cellular and overt rhythms. Given its importance to organismal performance and coordination with external environment, it is not surprising that the circadian clock is believed to be ubiquitous in invertebrates. This chapter will discuss the evolution and molecular designs of the invertebrate circadian clocks and describe our current understanding of the circadian clock neuronal network responsible for interpreting external temporal cues and coordinating cellular and physiological rhythms.

Out of breath, out of time: interactions between HIF and circadian rhythms

2020 ◽  
Vol 319 (3) ◽  
pp. C533-C540
Author(s):  
Emma J. O’Connell ◽  
Chloe-Anne Martinez ◽  
Yichuan G. Liang ◽  
Peter A. Cistulli ◽  
Kristina M. Cook
Keyword(s):  
Circadian Clock ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Cellular Level ◽  
The Body ◽  
Circadian Clocks ◽  
Molecular Clocks ◽  
Circadian Transcription ◽  
New Strategies

Humans have internal circadian clocks that ensure that important physiological functions occur at specific times of the day. These molecular clocks are regulated at the genomic level and exist in most cells of the body. Multiple circadian resetting cues have been identified, including light, temperature, and food. Recently, oxygen has been identified as a resetting cue, and emerging science indicates that this occurs through interactions at the cellular level between the circadian transcription-translation feedback loop and the hypoxia-inducible pathway (hypoxia-inducible factor; subject of the 2019 Nobel Prize in Physiology or Medicine). This review will cover recently identified relationships between HIF and proteins of the circadian clock. Interactions between the circadian clock and hypoxia could have wide-reaching implications for human diseases, and understanding the molecular mechanisms regulating these overlapping pathways may open up new strategies for drug discovery.

Circadian rhythms in a nutshell

2000 ◽  
Vol 3 (2) ◽  
pp. 59-74 ◽  
Author(s):  
ISAAC EDERY
Keyword(s):  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Life Forms ◽  
Circadian Clocks ◽  
Model Systems ◽  
Circadian Timing System ◽  
Environmental Transitions ◽  
Rotation Of The Earth ◽  
Living Organisms

Edery, Isaac. Circadian rhythms in a nutshell. Physiol Genomics 3: 59–74, 2000.—Living organisms on this planet have adapted to the daily rotation of the earth on its axis. By means of endogenous circadian clocks that can be synchronized to the daily and seasonal changes in external time cues, most notably light and temperature, life forms anticipate environmental transitions, perform activities at biologically advantageous times during the day, and undergo characteristic seasonal responses. The effects of transmeridian flight and shift work are stark reminders that although modern technologies can create “cities that never sleep” we cannot escape the recalcitrance of endogenous clocks that regulate much of our physiology and behavior. Moreover, malfunctions in the human circadian timing system are implicated in several disorders, including chronic sleep disorders in the elderly, manic-depression, and seasonal affective disorders (SAD or winter depression). Recent progress in understanding the molecular mechanisms underlying circadian rhythms has been remarkable. In its most basic form, circadian clocks are comprised of a set of proteins that, by virtue of the design principles involved, generate a self-sustaining transcriptional-translational feedback loop with a free-running period of about 24 h. One or more of the clock components is acutely sensitive to light, resulting in an oscillator that can be synchronized to local time. This review provides an overview of the roles circadian clocks play in nature, how they might have arisen, human health concerns related to clock dysfunction, and mainly focuses on the clockworks found in Drosophila and mice, the two best studied animal model systems for understanding the biochemical and cellular bases of circadian rhythms.

scholarly journals SDC mediates DNA methylation-controlled clock pace by interacting with ZTL in Arabidopsis

2021 ◽  
Vol 49 (7) ◽  
pp. 3764-3780
Author(s):  
Wenwen Tian ◽  
Ruyi Wang ◽  
Cunpei Bo ◽  
Yingjun Yu ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Dna Methyltransferases ◽  
Feedback Loops ◽  
Circadian Clocks ◽  
Fine Tuning ◽  
Dna Hypomethylation ◽  
Proteolytic Cascade ◽  
Molecular Bases

Abstract Molecular bases of eukaryotic circadian clocks mainly rely on transcriptional-translational feedback loops (TTFLs), while epigenetic codes also play critical roles in fine-tuning circadian rhythms. However, unlike histone modification codes that play extensive and well-known roles in the regulation of circadian clocks, whether DNA methylation (5mC) can affect the circadian clock, and the associated underlying molecular mechanisms, remains largely unexplored in many organisms. Here we demonstrate that global genome DNA hypomethylation can significantly lengthen the circadian period of Arabidopsis. Transcriptomic and genetic evidence demonstrate that SUPPRESSOR OF drm1 drm2 cmt3 (SDC), encoding an F-box containing protein, is required for the DNA hypomethylation-tuned circadian clock. Moreover, SDC can physically interact with another F-box containing protein ZEITLUPE (ZTL) to diminish its accumulation. Genetic analysis further revealed that ZTL and its substrate TIMING OF CAB EXPRESSION 1 (TOC1) likely act downstream of DNA methyltransferases to control circadian rhythm. Together, our findings support the notion that DNA methylation is important to maintain proper circadian pace in Arabidopsis, and further established that SDC links DNA hypomethylation with a proteolytic cascade to assist in tuning the circadian clock.

Feeding melatonin enhances the phase shifting response to triazolam in both young and old golden hamsters

2002 ◽  
Vol 282 (5) ◽  
pp. R1382-R1388 ◽  
Author(s):  
Daniel E. Kolker ◽  
Susan Losee Olson ◽  
Jeanette Dutton-Boilek ◽  
Katherine M. Bennett ◽  
Edward P. Wallen ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Activity Rhythm ◽  
Age Groups ◽  
Phase Shifting ◽  
Melatonin Secretion ◽  
Melatonin Treatment ◽  
Age Related ◽  
Circadian Time ◽  
Timing System ◽  
Circadian Timing System

Aging alters many aspects of circadian rhythmicity, including responsivity to phase-shifting stimuli and the amplitude of the rhythm of melatonin secretion. As melatonin is both an output from and an input to the circadian clock, we hypothesized that the decreased melatonin levels exhibited by old hamsters may adversely impact the circadian system as a whole. We enhanced the diurnal rhythm of melatonin by feeding melatonin to young and old hamsters. Animals of both age groups on the melatonin diet showed larger phase shifts than control-fed animals in response to an injection with the benzodiazepine triazolam at a circadian time known to induce phase advances in the activity rhythm of young animals. Thus melatonin treatment can increase the sensitivity of the circadian timing system of young animals to a nonphotic stimulus, and the ability to increase this sensitivity persists into old age, indicating exogenous melatonin might be useful in reversing at least some age-related changes in circadian clock function.

scholarly journals Chronic Light Cycle Disruption Alters Central Insulin and Leptin Signaling as well as Metabolic Markers in Male Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2257-2270 ◽  
Author(s):  
Nathan J Skinner ◽  
Mohammed Z Rizwan ◽  
David R Grattan ◽  
Alexander Tups
Keyword(s):  
Insulin Signaling ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Fasting Blood Glucose ◽  
Light Cycle ◽  
Metabolic Markers ◽  
Circadian Timing ◽  
Leptin Signaling ◽  
Timing System ◽  
Circadian Timing System

Abstract Recent evidence suggests that the circadian timing system plays a role in energy and glucose homeostasis, and disruptions to this system are a risk factor for the development of metabolic disorders. We exposed animals to a constantly shifting lighting environment comprised of a 6-hour advance, occurring every 6 days, to chronically disrupt their circadian timing system. This treatment caused a gradual increase in body weight of 12 ± 2% after 12 phase shifts, compared with a 6 ± 1% increase in mice under control lighting conditions. Additionally, after the fifth phase shift, light cycle–disrupted (CD) animals showed a reversal in their diurnal pattern of energy homeostasis and locomotor activity, followed by a subsequent loss of this rhythm. To investigate potential molecular mechanisms mediating these metabolic alterations, we assessed central leptin and insulin sensitivity. We discovered that CD mice had a decrease in central leptin signaling, as indicated by a reduction in the number of phosphorylated signal transducer and activator of transcription 3 immunoreactive cells in the arcuate nucleus of the hypothalamus. Furthermore, CD animals exhibited a marked increase in fasting blood glucose (269.4 ± 21.1 mg/dL) compared with controls (108.8 ± 21.3 mg/dL). This dramatic increase in fasting glucose levels was not associated with an increase in insulin levels, suggesting impairments in pancreatic insulin release. Peripheral hyperglycemia was accompanied by central alterations in insulin signaling at the level of phospho Akt and insulin receptor substrate 1, suggesting that light cycle disruption alters central insulin signaling. These results provide mechanistic insights into the association between light cycle disruption and metabolic disease.

Daily exercise facilitates phase delays of circadian melatonin rhythm in very dim light

2004 ◽  
Vol 286 (6) ◽  
pp. R1077-R1084 ◽  
Author(s):  
Laura K. Barger ◽  
Kenneth P. Wright ◽  
Rod J. Hughes ◽  
Charles A. Czeisler
Keyword(s):  
Exercise Intervention ◽  
Light Exposure ◽  
Phase Relationship ◽  
Shift Workers ◽  
Circadian Phase ◽  
Daily Exercise ◽  
Timing System ◽  
Before And After ◽  
Circadian Timing System ◽  
Dim Light

Shift workers and transmeridian travelers are exposed to abnormal work-rest cycles, inducing a change in the phase relationship between the sleep-wake cycle and the endogenous circadian timing system. Misalignment of circadian phase is associated with sleep disruption and deterioration of alertness and cognitive performance. Exercise has been investigated as a behavioral countermeasure to facilitate circadian adaptation. In contrast to previous studies where results might have been confounded by ambient light exposure, this investigation was conducted under strictly controlled very dim light (standing ∼0.65 lux; angle of gaze) conditions to minimize the phase-resetting effects of light. Eighteen young, fit males completed a 15-day randomized clinical trial in which circadian phase was measured in a constant routine before and after exposure to a week of nightly bouts of exercise or a nonexercise control condition after a 9-h delay in the sleep-wake schedule. Plasma samples collected every 30–60 min were analyzed for melatonin to determine circadian phase. Subjects who completed three 45-min bouts of cycle ergometry each night showed a significantly greater shift in the dim light melatonin onset (DLMO25%), dim light melatonin offset, and midpoint of the melatonin profile compared with nonexercising controls (Student t-test; P < 0.05). The magnitude of phase delay induced by the exercise intervention was significantly dependent on the relative timing of the exercise after the preintervention DLMO25% ( r = −0.73, P < 0.05) such that the closer to the DLMO25%, the greater the phase shift. These data suggest that exercise may help to facilitate circadian adaptation to schedules requiring a delay in the sleep-wake cycle.

scholarly journals Picrotoxin dramatically speeds the mammalian circadian clock independent of Cys-loop receptors

2013 ◽  
Vol 110 (1) ◽  
pp. 103-108 ◽  
Author(s):  
G. Mark Freeman ◽  
Masato Nakajima ◽  
Hiroki R. Ueda ◽  
Erik D. Herzog
Keyword(s):  
Synaptic Plasticity ◽  
Circadian Clock ◽  
Protein Stability ◽  
Genetic Manipulation ◽  
Cell Types ◽  
Cell Physiology ◽  
Timing System ◽  
Circadian Timing System ◽  
Rodent Cell ◽  
Novel Target

Picrotoxin is extensively and specifically used to inhibit GABAA receptors and other members of the Cys-loop receptor superfamily. We find that picrotoxin acts independently of known Cys-loop receptors to shorten the period of the circadian clock markedly by specifically advancing the accumulation of PERIOD2 protein. We show that this mechanism is surprisingly tetrodotoxin-insensitive, and the effect is larger than any known chemical or genetic manipulation. Notably, our results indicate that the circadian target of picrotoxin is common to a variety of human and rodent cell types but not Drosophila, thereby ruling out all conserved Cys-loop receptors and known regulators of mammalian PERIOD protein stability. Given that the circadian clock modulates significant aspects of cell physiology including synaptic plasticity, these results have immediate and broad experimental implications. Furthermore, our data point to the existence of an important and novel target within the mammalian circadian timing system.

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