Entrainment of circadian clocks in mammals by arousal and food

2011 ◽  
Vol 49 ◽  
pp. 119-136 ◽  
Author(s):  
Ralph E Mistlberger ◽  
Michael C Antle
Keyword(s):  
Clock Gene ◽  
Gene Mutations ◽  
Circadian System ◽  
Neural Pathways ◽  
Suprachiasmatic Nuclei ◽  
Social Stimuli ◽  
Clock Gene Expression ◽  
Circadian Oscillators ◽  
External Time ◽  
The Brain

Circadian rhythms in mammals are regulated by a system of endogenous circadian oscillators (clock cells) in the brain and in most peripheral organs and tissues. One group of clock cells in the hypothalamic SCN (suprachiasmatic nuclei) functions as a pacemaker for co-ordinating the timing of oscillators elsewhere in the brain and body. This master clock can be reset and entrained by daily LD (light–dark) cycles and thereby also serves to interface internal with external time, ensuring an appropriate alignment of behavioural and physiological rhythms with the solar day. Two features of the mammalian circadian system provide flexibility in circadian programming to exploit temporal regularities of social stimuli or food availability. One feature is the sensitivity of the SCN pacemaker to behavioural arousal stimulated during the usual sleep period, which can reset its phase and modulate its response to LD stimuli. Neural pathways from the brainstem and thalamus mediate these effects by releasing neurochemicals that inhibit retinal inputs to the SCN clock or that alter clock-gene expression in SCN clock cells. A second feature is the sensitivity of circadian oscillators outside of the SCN to stimuli associated with food intake, which enables animals to uncouple rhythms of behaviour and physiology from LD cycles and align these with predictable daily mealtimes. The location of oscillators necessary for food-entrained behavioural rhythms is not yet certain. Persistence of these rhythms in mice with clock-gene mutations that disable the SCN pacemaker suggests diversity in the molecular basis of light- and food-entrainable clocks.

scholarly journals Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase

2010 ◽  
Vol 299 (3) ◽  
pp. R751-R761 ◽  
Author(s):  
Carrie E. Mahoney ◽  
Daniel Brewer ◽  
Mary K. Costello ◽  
Judy McKinley Brewer ◽  
Eric L. Bittman
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Adrenal Medulla ◽  
Neural Control ◽  
Clock Gene ◽  
Neural Pathways ◽  
Peripheral Organs ◽  
Peripheral Oscillators ◽  
Clock Gene Expression ◽  
Oscillator Phase

To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio of haPer1, haPer2, and haBmal1 mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO). We also calculated expression on the sides ipsilateral vs. contralateral (I/C) to the side of the suprachiasmatic nucleus (SCN) expressing higher haPer1. The extent of asymmetry in split hamsters varied between specific genes, phases, and organs. Although the magnitude of asymmetry in peripheral organs was never as great as that in the SCN, we observed significantly greater lateralization of clock gene expression in the adrenal medulla and cortex, lung, and skeletal muscle, but not in liver or kidney, of split hamsters than of unsplit controls. We observed fivefold lateralization of expression of the clock-controlled gene, albumin site D-element binding protein ( Dbp), in skeletal muscle (H/L: 10.7 ± 3.7 at 3 h vs. 2.2 ± 0.3 at 0 h pAO; P = 0.03). Furthermore, tyrosine hydroxylase expression was asymmetrical in the adrenal medulla of split (H/L: 1.9 ± 0.5 at 0 h) vs. unsplit hamsters (1.2 ± 0.04; P < 0.05). Consistent with a model of neurally controlled gene expression, we found significant correlations between the phase angle between morning and evening components (ψme) and the level of asymmetry (H/L or I/C). Our results indicate that neural pathways contribute to, but cannot completely account for, SCN regulation of the phase of peripheral oscillators.

scholarly journals Physiology of Circadian Entrainment

2010 ◽  
Vol 90 (3) ◽  
pp. 1063-1102 ◽  
Author(s):  
Diego A. Golombek ◽  
Ruth E. Rosenstein
Keyword(s):  
Circadian Rhythms ◽  
Clock Gene ◽  
Retinal Diseases ◽  
Suprachiasmatic Nuclei ◽  
Circadian Variations ◽  
Dark Cycle ◽  
Clock Gene Expression ◽  
Biological Oscillators ◽  
Pituitary Adenylate Cyclase ◽  
Neurotransmitter Glutamate

Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since the period of this oscillation is of ∼24 h, to keep synchrony with the environment, circadian rhythms need to be entrained daily by means of Zeitgeber (“time giver”) signals, such as the light-dark cycle. Recent advances in the neurophysiology and molecular biology of circadian rhythmicity allow a better understanding of synchronization. In this review we cover several aspects of the mechanisms for photic entrainment of mammalian circadian rhythms, including retinal sensitivity to light by means of novel photopigments as well as circadian variations in the retina that contribute to the regulation of retinal physiology. Downstream from the retina, we examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction with SCN receptors and the resulting signal transduction pathways in suprachiasmatic neurons, as well as putative neuron-glia interactions. Finally, we describe and analyze clock gene expression and its importance in entrainment mechanisms, as well as circadian disorders or retinal diseases related to entrainment deficits, including experimental and clinical treatments.

scholarly journals Clock Gene Expression in Adult Primate Suprachiasmatic Nuclei and Adrenal: Is the Adrenal a Peripheral Clock Responsive to Melatonin?

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1454-1461 ◽  
Author(s):  
F. J. Valenzuela ◽  
C. Torres-Farfan ◽  
H. G. Richter ◽  
N. Mendez ◽  
C. Campino ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Clock Gene ◽  
Clock Genes ◽  
Phase Relationship ◽  
Suprachiasmatic Nuclei ◽  
Rhythmic Expression ◽  
Peripheral Oscillators ◽  
Clock Gene Expression ◽  
Timing System ◽  
Circadian Timing System

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.

scholarly journals Flies, clocks and evolution

2001 ◽  
Vol 356 (1415) ◽  
pp. 1769-1778 ◽  
Author(s):  
Ezio Rosato ◽  
Charalambos P. Kyriacou
Keyword(s):  
Gene Regulation ◽  
Negative Feedback ◽  
Clock Gene ◽  
Circadian System ◽  
Gene Duplications ◽  
Closely Related Species ◽  
Feedback Model ◽  
Silk Moth ◽  
The Brain

The negative feedback model for gene regulation of the circadian mechanism is described for the fruitfly, Drosophila melanogaster . The conservation of function of clock molecules is illustrated by comparison with the mammalian circadian system, and the apparent swapping of roles between various canonical clock gene components is highlighted. The role of clock gene duplications and divergence of function is introduced via the timeless gene. The impressive similarities in clock gene regulation between flies and mammals could suggest that variation between more closely related species within insects might be minimal. However, this is not borne out because the expression of clock molecules in the brain of the giant silk moth, Antheraea pernyi , is not easy to reconcile with the negative feedback roles of the period and timeless genes. Variation in clock gene sequences between and within fly species is examined and the role of co-evolution between and within clock molecules is described, particularly with reference to adaptive functions of the circadian phenotype.

Endogenous clock gene expression in the suprachiasmatic nuclei of previsual newborn rabbits is entrained by nursing

2009 ◽  
Vol 69 (1) ◽  
pp. 47-59 ◽  
Author(s):  
Ivette Caldelas ◽  
Belén González ◽  
Rodrigo Montúfar-Chaveznava ◽  
Robyn Hudson
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Suprachiasmatic Nuclei ◽  
Clock Gene Expression ◽  
Endogenous Clock

scholarly journals Circadian influences on dopamine circuits of the brain: regulation of striatal rhythms of clock gene expression and implications for psychopathology and disease

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2062 ◽  
Author(s):  
Michael Verwey ◽  
Sabine Dhir ◽  
Shimon Amir
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Gene ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Physiological Importance ◽  
Clock Gene Expression ◽  
Dopamine Circuits ◽  
The Brain

Circadian clock proteins form an autoregulatory feedback loop that is central to the endogenous generation and transmission of daily rhythms in behavior and physiology. Increasingly, circadian rhythms in clock gene expression are being reported in diverse tissues and brain regions that lie outside of the suprachiasmatic nucleus (SCN), the master circadian clock in mammals. For many of these extra-SCN rhythms, however, the region-specific implications are still emerging. In order to gain important insights into the potential behavioral, physiological, and psychological relevance of these daily oscillations, researchers have begun to focus on describing the neurochemical, hormonal, metabolic, and epigenetic contributions to the regulation of these rhythms. This review will highlight important sites and sources of circadian control within dopaminergic and striatal circuitries of the brain and will discuss potential implications for psychopathology and disease. For example, rhythms in clock gene expression in the dorsal striatum are sensitive to changes in dopamine release, which has potential implications for Parkinson’s disease and drug addiction. Rhythms in the ventral striatum and limbic forebrain are sensitive to psychological and physical stressors, which may have implications for major depressive disorder. Collectively, a rich circadian tapestry has emerged that forces us to expand traditional views and to reconsider the psychopathological, behavioral, and physiological importance of these region-specific rhythms in brain areas that are not immediately linked with the regulation of circadian rhythms.

scholarly journals Photic Entrainment of the Circadian System

2022 ◽  
Vol 23 (2) ◽  
pp. 729
Author(s):  
Anna Ashton ◽  
Russell G. Foster ◽  
Aarti Jagannath
Keyword(s):  
Circadian Clock ◽  
Molecular Basis ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
External World ◽  
Circadian System ◽  
Suprachiasmatic Nuclei ◽  
Photic Entrainment ◽  
External Time ◽  
Daily Changes

Circadian rhythms are essential for the survival of all organisms, enabling them to predict daily changes in the environment and time their behaviour appropriately. The molecular basis of such rhythms is the circadian clock, a self-sustaining molecular oscillator comprising a transcriptional–translational feedback loop. This must be continually readjusted to remain in alignment with the external world through a process termed entrainment, in which the phase of the master circadian clock in the suprachiasmatic nuclei (SCN) is adjusted in response to external time cues. In mammals, the primary time cue, or “zeitgeber”, is light, which inputs directly to the SCN where it is integrated with additional non-photic zeitgebers. The molecular mechanisms underlying photic entrainment are complex, comprising a number of regulatory factors. This review will outline the photoreception pathways mediating photic entrainment, and our current understanding of the molecular pathways that drive it in the SCN.

scholarly journals Comparison of expression patterns of six canonical clock genes of follicular phase and luteal phase in Small-tailed Han sheep

2021 ◽  
Vol 64 (2) ◽  
pp. 457-466
Author(s):  
Qi Han ◽  
Xiaoyun He ◽  
Ran Di ◽  
Mingxing Chu
Keyword(s):  
Gene Expression ◽  
Estrous Cycle ◽  
Luteal Phase ◽  
Clock Gene ◽  
Clock Genes ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Clock Gene Expression ◽  
The Relationship ◽  
The Brain

Abstract. The circadian rhythm is a biological rhythm that is closely related to the rhythmic expression of a series of clock genes. Results from several studies have indicated that clock genes are associated with the estrous cycle in female animals. Until now, the relationship between estrus cycle transition and clock gene expression in reproductive-axis-related tissues has remained unknown in Small-tailed Han (STH) sheep. This study was conducted to analyze the expression patterns of six canonical clock genes (Clock, BMAL1, Per1, Per2, Cry1, and Cry2) in the follicle phase and luteal phase of STH sheep. We found that all six genes were expressed in the brain, cerebellum, hypothalamus, pituitary, ovary, uterus, and oviduct in follicle and luteal phases. The results indicated that Clock expression was significantly higher in the cerebellum, hypothalamus, and uterus of the luteal phase than that of the follicle phase, whereas BMAL1 expression was significantly higher in the hypothalamus of the luteal phase than that of the follicle phase. Per1 expression was significantly higher in the brain, cerebellum, hypothalamus, and pituitary of the luteal phase than that of the follicle phase, and Per2 expression was significantly higher in the hypothalamus, pituitary, and uterus of the luteal phase than that of the follicle phase. Cry1 expression was significantly higher in the brain, cerebellum, and hypothalamus of the luteal phase than that of the follicle phase, whereas Cry2 expression was significantly higher in the pituitary of the luteal phase than that of the follicle phase. The clock gene expression in all tissues was different between follicle and luteal phases, but all clock gene mRNA levels were found to exhibit higher expression among seven tissues in the luteal phase. Our results suggest that estrous cycles may be associated with clock gene expression in the STH sheep. This is the first study to systematically analyze the expression patterns of clock genes of different estrous cycle in ewes, which could form a basis for further studies to develop the relationship between clock genes and the estrous cycle.

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