Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice

Jagannath, Aarti; Varga, Norbert; Dallmann, Robert; Rando, Gianpaolo; Gosselin, Pauline; Ebrahimjee, Farid; Taylor, Lewis; Mosneagu, Dragos I; Stefaniak, Jakub; Walsh, Steven; Palumaa, Teele; Pretoro, Simona Di; Sanghani, Harshmeena; Wakaf, Zeinab; Churchill, Grant C.; Galione, Antony; Peirson, Stuart N.; Boison, Detlev; Brown, Steven A.; Foster, Russell G.; Vasudevan, Sridhar

doi:10.1038/s41467-021-22179-z

Cited by 79 publications

(78 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Per1 is rapidly upregulated within 30 min of light exposure, whereas Per2 induction is slower with a timeframe of several hours [ 44 ]. Recent evidence suggests this is due to the induction of Per1 by CREB, and the induction of Per2 by a parallel pathway involving the activation of ERK1/2 by Ca 2+ influx, leading to upregulation of the immediate-early transcription factors JUN and FOS [ 52 ]. These then heterodimerise to form AP-1, which drives Per2 transcription and other genes containing AP-1 response elements ( Figure 3 ).…”

Section: Molecular Photoentrainment Of the Suprachiasmatic Nuclei (Scn)mentioning

confidence: 99%

“…Such G protein-coupled receptor (GPCR) signalling converges on the same pathways that are activated by light, specifically cAMP-CREB and Ca 2+ -ERK1/2-AP-1, thus resulting in Per1/2 upregulation. As the A 1 receptor is the dominant form within the SCN, elevated adenosine, as occurs following sleep deprivation, inhibits the effect of light on the circadian system ( Figure 3 ), whilst adenosine A 1 /A 2A antagonists enhance photic responses [ 52 ]. Caffeine, which has A 1 /A 2A antagonism properties, both enhances photic shifts in humans and counters the effects of sleep deprivation on the clock in mice [ 52 , 63 , 68 , 69 ].…”

Section: Gating the Light Sensitivity Of The Clockmentioning

confidence: 99%

“…As the A 1 receptor is the dominant form within the SCN, elevated adenosine, as occurs following sleep deprivation, inhibits the effect of light on the circadian system ( Figure 3 ), whilst adenosine A 1 /A 2A antagonists enhance photic responses [ 52 ]. Caffeine, which has A 1 /A 2A antagonism properties, both enhances photic shifts in humans and counters the effects of sleep deprivation on the clock in mice [ 52 , 63 , 68 , 69 ]. This pathway provides a molecular framework by which the major drives that control sleep/wake transitions interact, namely the circadian (Process C) and homeostatic (Process S) drives [ 70 , 71 ], thus allowing sleep history to shape photic entrainment processes [ 52 ].…”

Section: Gating the Light Sensitivity Of The Clockmentioning

confidence: 99%

See 2 more Smart Citations

Photic Entrainment of the Circadian System

Ashton

Foster

Jagannath

2022

IJMS

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Molecular Photoentrainment Of the Suprachiasmatic Nuclei (Scn)mentioning

confidence: 99%

Section: Gating the Light Sensitivity Of The Clockmentioning

confidence: 99%

Section: Gating the Light Sensitivity Of The Clockmentioning

confidence: 99%

See 1 more Smart Citation

Photic Entrainment of the Circadian System

Ashton

Foster

Jagannath

2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…These findings suggest that caffeine may influence the circadian timing system. In the mammalian circadian pacemaker, caffeine acts primarily through the Adenosine receptor A1 and thus modulates cAMP signalling, the core component of cellular circadian clock [44][45][46] . However adult-stage specific caffeine treatment mediated wakefulness was shown to be independent of adenosine receptor in Drosophila and enhanced cAMP/PKA signalling is partly involved in this adult stage specific caffeine mediated wakefulness 29 .…”

Section: Discussionmentioning

confidence: 99%

The duration of caffeine treatment plays an essential role in its effect on sleep and circadian rhythm

Segu

Kannan

2021

Preprint

View full text Add to dashboard Cite

The circadian clock governs the timing of sleep-wake cycles as well as of other behavioural, physiological and metabolic processes. While the endogenous circadian clock mediates the timing of sleep, homeostatic mechanisms modulate the amount and depth of sleep. Evidence from previous studies showed that caffeine intake promotes wakefulness, whereas adult-stage specific caffeine treatment not only suppresses sleep but also delays the phase of circadian rhythm in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on circadian and homeostatic regulation of sleep. In the present study we examined the differential effect of acute and chronic caffeine treatment on sleep ontogeny as well as on circadian and homeostatic regulation of sleep in Drosophila. The results of our study showed that acute caffeine treatment reduces day and night sleep in mature flies through the homeostatic pathway whereas it reduced only the day sleep in young flies. Chronic caffeine treatment did not exert any significant effect on sleep in young flies. On the other hand, it delayed the timing of sleep in mature flies and in addition flies under higher caffeine concentration reduced the morning and evening anticipatory activity under 12 hour: 12 hour light: dark cycles. These flies also exhibited either a longer free running period or arrhythmicity under constant darkness. The results of our study showed that acute caffeine treatment suppresses sleep through the homeostatic pathway whereas prolonged caffeine treatment disrupts the circadian rhythm in mature flies.

show abstract

“…G-protein coupled receptors (GPCRs) are the largest family of cell surface receptors in eukaryotic cells. These seven-transmembrane receptors have influence in physiological events such as cell to cell communication, immune responses, nerve transmission and even hunger and sleep regulation [1][2][3]. The role of GPCRs in diseases such as rheumatoid arthritis, heart disease, cancer, obesity, and neurodegenerative disorders accentuates the need to investigate this family of receptors further.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Super-Resolution Imaging for the Analysis of GPCR Oligomerization

et al. 2021

View full text Add to dashboard Cite

G-protein coupled receptors (GPCRs) are known to form homo- and hetero- oligomers which are considered critical to modulate their function. However, studying the existence and functional implication of these complexes is not straightforward as controversial results are obtained depending on the method of analysis employed. Here, we use a quantitative single molecule super-resolution imaging technique named qPAINT to quantify complex formation within an example GPCR. qPAINT, based upon DNA-PAINT, takes advantage of the binding kinetics between fluorescently labelled DNA imager strands to complementary DNA docking strands coupled to protein targeting antibodies to quantify the protein copy number in nanoscale dimensions. We demonstrate qPAINT analysis via a novel pipeline to study the oligomerization of the purinergic receptor Y2 (P2Y2), a rhodopsin-like GPCR, highly expressed in the pancreatic cancer cell line AsPC-1, under control, agonistic and antagonistic conditions. Results reveal that whilst the density of P2Y2 receptors remained unchanged, antagonistic conditions displayed reduced percentage of oligomers, and smaller numbers of receptors in complexes. Yet, the oligomeric state of the receptors was not affected by agonist treatment, in line with previous reports. Understanding P2Y2 oligomerization under agonistic and antagonistic conditions will contribute to unravelling P2Y2 mechanistic action and therapeutic targeting.

show abstract

Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice

Cited by 79 publications

References 60 publications

Photic Entrainment of the Circadian System

Photic Entrainment of the Circadian System

The duration of caffeine treatment plays an essential role in its effect on sleep and circadian rhythm

Quantitative Super-Resolution Imaging for the Analysis of GPCR Oligomerization

Contact Info

Product

Resources

About