Effects of caffeine on circadian phase, amplitude and period evaluated in cells in vitro and peripheral organs in vivo in PER2:LUCIFERASE mice. (24th November 2014)

• Record Type: Journal Article
• Authors: Narishige, Seira; Kuwahara, Mari; Shinozaki, Ayako; Okada, Satoshi; Ikeda, Yuko; Kamagata, Mayo; Tahara, Yu; Shibata, Shigenobu
• Is Part Of: British journal of pharmacology. Volume 171:Number 24(2014:Dec.)
• Page Start: 5858
• Page End: 5869
• Publication Date: 2014-11-24
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12890
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12890-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Caffeine is one of the most commonly used psychoactive substances. Circadian rhythms consist of the main suprachiasmatic nucleus (SCN) clocks and peripheral clocks. Although caffeine lengthens circadian rhythms and modifies phase changes in SCN‐operated rhythms, the effects on caffeine on the phase, period and amplitude of peripheral organ clocks are not known. In addition, the role of cAMP/Ca<sup>2+</sup> signalling in effects of caffeine on rhythm has not been fully elucidated.</p> </sec> <sec id="bph12890-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>We examined whether chronic or transient application of caffeine affects circadian period/amplitude and phase by evaluating bioluminescence rhythm in PER2::LUCIFERASE knock‐in mice. Circadian rhythms were monitored <italic>in vitro</italic> using fibroblasts and <italic>ex vivo</italic> and <italic>in vivo</italic> for monitoring of peripheral clocks.</p> </sec> <sec id="bph12890-sec-0003" sec-type="section"> <title>Key Results</title> <p>Chronic application of caffeine (0.1–10 mM) increased period and amplitude <italic>in vitro</italic>. Transient application of caffeine (10 mM) near the bottom of the decreasing phase of bioluminescence rhythm caused phase advance <italic>in vitro</italic>. Caffeine (0.1%) intake caused a phase delay under light–dark or constant dark conditions, suggesting a period‐lengthening effect <italic>in vivo</italic>. Caffeine (20 mg·kg<sup>−1</sup>) at daytime or at late night‐time caused phase advance or delay in bioluminescence rhythm in the liver and kidney respectively. The complicated roles of cAMP/Ca<sup>2+</sup> signalling may be involved in the caffeine‐induced increase of period and amplitude <italic>in vitro</italic>.</p> </sec> <sec id="bph12890-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>Caffeine affects circadian rhythm in mice by lengthening the period and causing a phase shift of peripheral clocks. These results suggest that caffeine intake with food/drink may help with food‐induced resetting of peripheral circadian clocks.</p> </sec> </abstract>