Caffeine increases light responsiveness of the mouse circadian pacemaker

Diepen, Hester C. van; Lucassen, Eliane A.; Yasenkov, Roman; Groenen, Inske; IJzerman, Adriaan P.; Meijer, Johanna H.; Deboer, Tom

doi:10.1111/ejn.12715

Cited by 58 publications

(78 citation statements)

References 59 publications

(73 reference statements)

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“…For example, under very low levels of basal arousal, light could be ineffective, but this effect can be restored by caffeine administration [19]. In agreement with the latter study, our results revealed a positive relationship between arousal and lighting effects.…”

Section: Discussionsupporting

confidence: 90%

“…In particular, the presentation of a novel stimulus presumed to increase arousal in hamsters (a new running wheel), attenuated the synchronizing effect of light on circadian rhythms [18]. Moreover, extremely low basal arousal induced by sleep deprivation can block the alerting effect of light upon the activity of suprachiasmatic nuclei, but this effect can be restored by increasing arousal through administration of caffeine [19,20, 21]. …”

Section: Introductionmentioning

confidence: 99%

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Light Effects on Behavioural Performance Depend on the Individual State of Vigilance

2016

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Research has shown that exposure to bright white light or blue-enriched light enhances alertness, but this effect is not consistently observed in tasks demanding high-level cognition (e.g., Sustained Attention to Response Task—SART, which measures inhibitory control). Individual differences in sensitivity to light effects might be mediated by variations in the basal level of arousal. We tested this hypothesis by measuring the participants’ behavioural state of vigilance before light exposure, through the Psychomotor Vigilance Task. Then we compared the effects of a blue-enriched vs. dim light at nighttime on the performance of the auditory SART, by controlling for individual differences in basal arousal. The results replicated the alerting effects of blue-enriched light, as indexed by lower values of both proximal temperature and distal-proximal gradient. The main finding was that lighting effects on SART performance were highly variable across individuals and depended on their prior state of vigilance. Specifically, participants with higher levels of basal vigilance before light exposure benefited most from blue-enriched lighting, responding faster in the SART. These results highlight the importance of considering basal vigilance to define the boundary conditions of light effects on cognitive performance. Our study adds to current research delineating the complex and reciprocal interactions between lighting effects, arousal, cognitive task demands and behavioural performance.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Light Effects on Behavioural Performance Depend on the Individual State of Vigilance

2016

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“…To address this question directly, we employed an in vitro assay based upon bioluminescent reporters of circadian transcriptional rhythms in the well-characterized human U2OS cell line. Period-lengthening in response to chronic caffeine has been reported both at the behavioral level in rodents and flies (11,18,28 ) , as well as at the cellular level in isolated rodent SCN ex vivo and human U2OS cells in vitro (16,18). Human U2OS cells recapitulate the key observation under investigation (18) and similar to the SCN, primarily express the higher affinity, ubiquitous and abundant A 1 adenosine receptor (A 1 R, encoded by the ADORA1 gene) (29,30) as well as PDEs and ryanodine receptors.…”

Section: Resultsmentioning

confidence: 99%

“…For example, adenosine is reported to influence retinal function and transmission of photic information via the retinohypothalamic tract (RHT). Moreover, adenosine administration has been reported to attenuate phase shifts induced by light exposure (42) and caffeine has been shown to enhance the period lengthening effects of light in mice (28). Furthermore, adenosine receptor mRNA is expressed in retinal ganglion cells (43), however whether these include the melanopsin retinal ganglion cells that project to the SCN is unknown.…”

Section: Discussionmentioning

confidence: 99%

Effects of caffeine on the human circadian clock in vivo and in vitro

et al. 2015

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Caffeine’s wakefulness-promoting and sleep-disrupting effects are well established, yet whether caffeine affects human circadian timing is unknown. Here we show that evening caffeine consumption delays the human circadian melatonin rhythm in vivo, and chronic application of caffeine lengthens the circadian period of molecular oscillations in vitro primarily via an adenosine receptor/cyclic AMP-dependent mechanism. In a double-blind, placebo controlled, ~49-day long within-subject study, we found the equivalent amount of caffeine as that in a double espresso 3 hours before habitual bedtime induced a phase delay of the circadian melatonin rhythm in humans by ~40 minutes. This magnitude of delay was nearly half of the magnitude of the phase-delaying response induced by exposure to 3-hours of evening bright-light (~3000 lux; ~7 Watts/m2) that began at habitual bedtime. Furthermore, using human osteosarcoma U2OS cells expressing clock gene luciferase reporters, we found a dose-dependent lengthening of circadian period by caffeine. By pharmacological dissection and siRNA knockdown we established that perturbation of adenosine receptor signaling, but not ryanodine receptor or phosphodiesterase activity, is sufficient to account for caffeine’s effects on cellular timekeeping. We also used a cyclic AMP biosensor to show that caffeine increased cyclic AMP levels, indicating that caffeine can influence a core component of the cellular circadian clock. Taken together, our findings demonstrate that caffeine influences human circadian timing and gives new insight into how the world’s most widely consumed psychoactive drug impacts upon human physiology.

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“…Additionally, sleep deprivation is known to reduce light responsiveness of the SCN by lowering circadian phase-shifting capacity 85 and decreasing SCN neuronal activity 86, 87 . Thus, both light history and sleep deprivation may account for the rather limited melatonin suppression by constant light, and for the unchanged circadian markers in the study.…”

Section: Discussionmentioning

confidence: 99%

Differential impact in young and older individuals of blue-enriched white light on circadian physiology and alertness during sustained wakefulness

Gabel

Reichert

Maire

et al. 2017

Sci Rep

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We tested the effect of different lights as a countermeasure against sleep-loss decrements in alertness, melatonin and cortisol profile, skin temperature and wrist motor activity in healthy young and older volunteers under extendend wakefulness. 26 young [mean (SE): 25.0 (0.6) y)] and 12 older participants [(mean (SE): 63.6 (1.3) y)] underwent 40-h of sustained wakefulness during 3 balanced crossover segments, once under dim light (DL: 8 lx), and once under either white light (WL: 250 lx, 2,800 K) or blue-enriched white light (BL: 250 lx, 9,000 K) exposure. Subjective sleepiness, melatonin and cortisol were assessed hourly. Skin temperature and wrist motor activity were continuously recorded. WL and BL induced an alerting response in both the older (p = 0.005) and the young participants (p = 0.021). The evening rise in melatonin was attentuated under both WL and BL only in the young. Cortisol levels were increased and activity levels decreased in the older compared to the young only under BL (p = 0.0003). Compared to the young, both proximal and distal skin temperatures were lower in older participants under all lighting conditions. Thus the color temperature of normal intensity lighting may have differential effects on circadian physiology in young and older individuals.

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Caffeine increases light responsiveness of the mouse circadian pacemaker

Cited by 58 publications

References 59 publications

Light Effects on Behavioural Performance Depend on the Individual State of Vigilance

Light Effects on Behavioural Performance Depend on the Individual State of Vigilance

Effects of caffeine on the human circadian clock in vivo and in vitro

Differential impact in young and older individuals of blue-enriched white light on circadian physiology and alertness during sustained wakefulness

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