Differential cAMP Gating of Glutamatergic Signaling Regulates Long-Term State Changes in the Suprachiasmatic Circadian Clock

Tischkau, Shelley A.; Gallman, Eve A.; Buchanan, Gordon F.; Gillette, Martha U.

doi:10.1523/jneurosci.20-20-07830.2000

Cited by 87 publications

(78 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the MC2R is a G s protein-coupled receptor linked to activation of adenylyl cyclase and cAMP generation (9,43), clock entrainment by ACTH may be cAMP-dependent. It is well established that cAMP is involved in resetting the SCN and peripheral clocks (33,34,37,48). Forskolin, an activator of adenylyl cyclase, produced a PRC similar to that of ACTH.…”

Section: Discussionmentioning

confidence: 94%

Phase-dependent resetting of the adrenal clock by ACTH in vitro

Yoder

Brandeland

Engeland

2014

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Yoder JM, Brandeland M, Engeland WC. Phase-dependent resetting of the adrenal clock by ACTH in vitro. Am J Physiol Regul Integr Comp Physiol 306: R387-R393, 2014. First published January 29, 2014 doi:10.1152/ajpregu.00519.2013The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoids, yet how the clock is synchronized to the external environment is unknown. Using mPER2::Luciferase (mPER2Luc) knockin mice, in which luciferase is rhythmically expressed under the control of the mouse Per2 clock gene, we hypothesized that ACTH transmits entrainment signals to the adrenal. Adrenal explants were administered ACTH at different phases of the mPER2Luc rhythm. Treatment with ACTH 1-39 produced a phase delay that was phase-dependent, with a maximum at circadian time (CT)18; ACTH did not alter the period or amplitude of the rhythm. Forskolin produced a parallel response, suggesting that the phase delay was cAMP-mediated. The response to ACTH was concentration-dependent and peptide-specific. Pulse administration (60 min) of ACTH 1-39 also produced phase delays restricted to late CTs. In contrast to ACTH 1-39, other ACTH fragments, including ␣-melanocyte-stimulating hormone, which do not activate the melanocortin 2 (MC2/ACTH) receptor, had no effect. The finding that ACTH in vitro phase delays the adrenal mPER2luc rhythm in a monophasic fashion argues for ACTH as a key resetter, but not the sole entrainer, of the adrenal clock. adrenal clock; adrenocorticotropic hormone; nonphotic entrainment THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) axis is characterized by a robust circadian variation in glucocorticoids. This rhythm is paralleled by rhythms in plasma ACTH (6), and adrenal sensitivity to ACTH (10) mediated, in part, by sympathetic activity (49). Rhythmic ACTH secretion is regulated by corticotropin-releasing hormone (CRH) from the hypothalamic paraventricular nucleus (PVN) (6). Circadian timing is dependent on a clock in the suprachiasmatic nucleus (SCN) (41) that is reset daily by photic information transmitted from the retina (28) with SCN neurons relaying these signals to the PVN (19). This mechanism guarantees that glucocorticoid rhythms are entrained to the daily light-dark (LD) cycle.A molecular clock exists in the SCN (39) and peripheral tissues (12), including the adrenal (4). The clock consists of interlocking feedback loops of gene transcription and translation (39). The "positive" limb involves CLOCK and BMAL1, which heterodimerize and activate transcription of period genes, Per1 and Per2, and cryptochrome genes, Cry1 and Cry2. The Per and Cry transcripts increase with the protein products, PER and CRY, functioning as the "negative limb" by forming heterodimers that act on the CLOCK:BMAL1 complex to repress their own transcription. The feedback loops are self-regulating with an ϳ24-h periodicity.The adrenal clock controls steroidogenesis by gating sensitivity to ACTH. In Per2/Cry1 mutant mice that lack a functioning clock, rhythms in adrenal sensitivity are absent and the cortico...

show abstract

Section: Discussionmentioning

confidence: 94%

Phase-dependent resetting of the adrenal clock by ACTH in vitro

Yoder

Brandeland

Engeland

2014

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Thus, these results strongly suggest that MAPK is a functional component in the SCN autonomous circadian system. Light-induced discharges in the SCN neurons may activate MAPK (Obrietan et al, 1999;Tischkau et al, 2000), thus implying the possibility that light-independent circadian discharges also function as upstream signals to activate MAPK in a circadian manner. The cAMP response element binding protein (CREB) is generally believed to be one of the downstream targets of activated MAPK in the SCN (Obrietan et al, 1999;Coogan and Piggins, 2004), and activated CREB may drive circadian transcription of clock genes such as Per1 (Travnickova-Bendova et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Mitogen-Activated Protein Kinase Is a Functional Component of the Autonomous Circadian System in the Suprachiasmatic Nucleus

et al. 2008

View full text Add to dashboard Cite

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker driving behavioral and physiological rhythms in mammals. Circadian activation of mitogen-activated protein kinase [MAPK; also known as ERK (extracellular signal-regulated kinase)] is observed in vivo in the SCN under constant darkness, although the biological significance of this remains unclear. To elucidate this question, we first examined whether MAPK was autonomously activated in ex vivo SCN slices. Moreover, we investigated the effect of MAPK inhibition on circadian clock gene expression and neuronal firing rhythms using SCN-slice culture systems. We show herein that MAPK is autonomously activated in the SCN, and our data demonstrate that inhibition of the MAPK activity results in dampened rhythms and reduced basal levels in circadian clock gene expression at the SCN single-neuron level. Furthermore, MAPK inhibition attenuates autonomous circadian neuronal firing rhythms in the SCN. Thus, our data suggest that light-independent MAPK activity contributes to the robustness of the SCN autonomous circadian system.

show abstract

“…Application of cAMP analogs in vitro induces prominent phase advances in the subjective day but not in the subjective night (22). Although there is also evidence that suggests a role for cAMP/PKA at night, this role appears to be to promote the effects of light/GLU in early night but to oppose them in late night (23).…”

mentioning

confidence: 99%

Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules

Agostino

Plano

Golombék

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Mammalian circadian rhythms are generated by a master clock located in the suprachiasmatic nuclei and entrained by lightactivated signaling pathways. In hamsters, the mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase, cGMP and its related kinase (PKG). It is not completely known whether interference with this pathway affects entrainment of the clock, including adaptation to changing light schedules. Here we report that cGMP-specific phosphodiesterase 5 is present in the hamster suprachiasmatic nuclei, and administration of the inhibitor sildenafil (3.5 mg/kg, i.p.) enhances circadian responses to light and decreases the amount of time necessary for reentrainment after phase advances of the light-dark cycle. These results suggest that sildenafil may be useful for treatment of circadian adaptation to environmental changes, including transmeridian eastbound flight schedules.cGMP phosphodiesterase ͉ resynchronization ͉ suprachiasmatic nuclei ͉ phase advance

show abstract

Differential cAMP Gating of Glutamatergic Signaling Regulates Long-Term State Changes in the Suprachiasmatic Circadian Clock

Cited by 87 publications

References 62 publications

Phase-dependent resetting of the adrenal clock by ACTH in vitro

Phase-dependent resetting of the adrenal clock by ACTH in vitro

Mitogen-Activated Protein Kinase Is a Functional Component of the Autonomous Circadian System in the Suprachiasmatic Nucleus

Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules

Contact Info

Product

Resources

About