scholarly journals Minireview: The Circadian Clockwork of the Suprachiasmatic Nuclei—Analysis of a Cellular Oscillator that Drives Endocrine Rhythms

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5624-5634 ◽  
Author(s):  
Elizabeth S. Maywood ◽  
John S. O’Neill ◽  
Johanna E. Chesham ◽  
Michael H. Hastings
Keyword(s):  
Neural Circuits ◽  
Clock Genes ◽  
Time Base ◽  
Suprachiasmatic Nuclei ◽  
Dark Cycle ◽  
Cellular Mechanisms ◽  
Circadian Control ◽  
Daily Cycles ◽  
Central Clock ◽  
Retinal Afferents

The secretion of hormones is temporally precise and periodic, oscillating over hours, days, and months. The circadian timekeeper within the suprachiasmatic nuclei (SCN) is central to this coordination, modulating the frequency of pulsatile release, maintaining daily cycles of secretion, and defining the time base for longer-term rhythms. This central clock is driven by cell-autonomous, transcriptional/posttranslational feedback loops incorporating Period (Per) and other clock genes. SCN neurons exist, however, within neural circuits, and an unresolved question is how SCN clock cells interact. By monitoring the SCN molecular clockwork using fluorescence and bioluminescence videomicroscopy of organotypic slices from mPer1::GFP and mPer1::luciferase transgenic mice, we show that interneuronal neuropeptidergic signaling via the vasoactive intestinal peptide (VIP)/PACAP2 (VPAC2) receptor for VIP (an abundant SCN neuropeptide) is necessary to maintain both the amplitude and the synchrony of clock cells in the SCN. Acute induction of mPer1 by light is, however, independent of VIP/VPAC2 signaling, demonstrating dissociation between cellular mechanisms mediating circadian control of the clockwork and those mediating its retinally dependent entrainment to the light/dark cycle. The latter likely involves the Ca2+/cAMP response elements of mPer genes, triggered by a MAPK cascade activated by retinal afferents to the SCN. In the absence of VPAC2 signaling, however, this cascade is inappropriately responsive to light during circadian daytime. Hence VPAC2-mediated signaling sustains the SCN cellular clockwork and is necessary both for interneuronal synchronization and appropriate entrainment to the light/dark cycle. In its absence, behavioral and endocrine rhythms are severely compromised.

The neural circadian system of mammals

2011 ◽  
Vol 49 ◽  
pp. 1-17 ◽  
Author(s):  
Hugh D. Piggins ◽  
Clare Guilding
Keyword(s):  
Circadian Rhythms ◽  
Circadian System ◽  
Daily Activities ◽  
Suprachiasmatic Nuclei ◽  
Dark Cycle ◽  
Environmental Light ◽  
Endogenous Clock ◽  
Central Clock

Humans and other mammals exhibit a remarkable array of cyclical changes in physiology and behaviour. These are often synchronized to the changing environmental light–dark cycle and persist in constant conditions. Such circadian rhythms are controlled by an endogenous clock, located in the suprachiasmatic nuclei of the hypothalamus. This structure and its cells have unique properties, and some of these are reviewed to highlight how this central clock controls and sculpts our daily activities.

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.

scholarly journals Minireview: Circadian Control of Metabolism by the Suprachiasmatic Nuclei

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5635-5639 ◽  
Author(s):  
Andries Kalsbeek ◽  
Felix Kreier ◽  
Eric Fliers ◽  
Hans P. Sauerwein ◽  
Johannes A. Romijn ◽  
...  
Keyword(s):  
Suprachiasmatic Nuclei ◽  
Circadian Control

scholarly journals An NF-κB–driven lncRNA orchestrates colitis and circadian clock

2020 ◽  
Vol 6 (42) ◽  
pp. eabb5202
Author(s):  
Shuai Wang ◽  
Yanke Lin ◽  
Feng Li ◽  
Zifei Qin ◽  
Ziyue Zhou ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Experimental Colitis ◽  
Circadian Clock Gene ◽  
Its Gene ◽  
E Box ◽  
Direct Binding ◽  
Central Clock ◽  
Clock Protein

We uncover a cycling and NF-κB–driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erbα, thereby linking circadian clock to colitis. Cycling expression of Lnc-UC is generated by the central clock protein Bmal1 via an E-box element. NF-κB activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two κB sites. Lnc-UC ablation disrupts colonic expressions of clock genes in mice; particularly, Rev-erbα is down-regulated and its diurnal rhythm is blunted. Consistently, Lnc-UC promotes expression of Rev-erbα (a known dual NF-κB/Nlrp3 repressor) to inactivate NF-κB signaling and Nlrp3 inflammasome in macrophages. Furthermore, Lnc-UC ablation sensitizes mice to experimental colitis and abolishes the diurnal rhythmicity in disease severity. Mechanistically, Lnc-UC physically interacts with Cbx1 protein to reduce its gene silencing activity via H3K9me3, thereby enhancing Rev-erbα transcription and expression. In addition, we identify a human Lnc-UC that has potential to promote Rev-erbα expression and restrain inflammations.

scholarly journals Role of DBP in the Circadian Oscillatory Mechanism

2000 ◽  
Vol 20 (13) ◽  
pp. 4773-4781 ◽  
Author(s):  
Shun Yamaguchi ◽  
Shigeru Mitsui ◽  
Lily Yan ◽  
Kazuhiro Yagita ◽  
Shigeru Miyake ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leucine Zipper ◽  
The Other ◽  
Suprachiasmatic Nuclei ◽  
Transcription Factor Family ◽  
Transcript Levels ◽  
Oscillatory Mechanism ◽  
Central Clock ◽  
E Boxes

ABSTRACT Transcript levels of DBP, a member of the PAR leucine zipper transcription factor family, exhibit a robust rhythm in suprachiasmatic nuclei, the mammalian circadian center. Here we report that DBP is able to activate the promoter of a putative clock oscillating gene,mPer1, by directly binding to the mPer1promoter. The mPer1 promoter is cooperatively activated by DBP and CLOCK-BMAL1. On the other hand, dbp transcription is activated by CLOCK-BMAL1 through E-boxes and inhibited by the mPER and mCRY proteins, as is the case for mPer1. Thus, a clock-controlled dbp gene may play an important role in central clock oscillation.

Disrupted light–dark cycle abolishes circadian expression of peripheral clock genes without inducing behavioral arrhythmicity in mice

2015 ◽  
Vol 458 (2) ◽  
pp. 256-261 ◽  
Author(s):  
Katsutaka Oishi ◽  
Sayaka Higo-Yamamoto ◽  
Saori Yamamoto ◽  
Yuki Yasumoto
Keyword(s):  
Clock Genes ◽  
Dark Cycle ◽  
Peripheral Clock ◽  
Circadian Expression

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.

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