Potent synchronization of peripheral circadian clocks by glucocorticoid injections in PER2::LUC-Clock/Clock mice

ABSTRACT

In mammals, the central clock (the suprachiasmatic nuclei, SCN) is entrained mainly by the light-dark cycle, whereas peripheral clocks in the peripheral tissues are entrained/synchronized by multiple factors, including feeding patterns and endocrine hormones such as glucocorticoids. Clock-mutant mice (Clock/Clock), which have a mutation in a core clock gene, show potent phase resetting in response to light pulses compared with wild-type (WT) mice, owing to the damped and flexible oscillator in the SCN. However, the phase resetting of the peripheral clocks in Clock/Clock mice has not been elucidated. Here, we characterized the peripheral clock gene synchronization in Clock/Clock mice by daily injections of a synthetic glucocorticoid (dexamethasone, DEX) by monitoring in vivo PER2::LUCIFERASE bioluminescence. Compared with WT mice, the Clock/Clock mice showed significantly decreased bioluminescence and peripheral clock rhythms with decreased amplitudes and delayed phases. In addition, the DEX injections increased the amplitudes and advanced the phases. In order to examine the robustness of the internal oscillator, T-cycle experiments involving DEX stimulations with 24- or 30-h intervals were performed. The Clock/Clock mice synchronized to the 30-h T-cycle stimulation, which suggested that the peripheral clocks in the Clock/Clock mice had increased synchronizing ability upon DEX stimulation, to that of circadian and hour-glass type oscillations, because of weak internal clock oscillators.

KEYWORDS:

• Circadian rhythm
• Clock mutation
• glucocorticoid
• synchronizing ability

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

This work was partially supported by the Council for Science, Technology and Innovation, SIP, “Technologies for creating next-generation agriculture, forestry, and fisheries” (funding agency: Bio-oriented Technology Research Advancement Institution, NARO) (S.S.), and by a Grant-in-Aid for Scientific Research (S) (26220201) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (S.S.).

Additional information

Funding

This work was partially supported by the Council for Science, Technology and Innovation, SIP, “Technologies for creating next-generation agriculture, forestry, and fisheries” (funding agency: Bio-oriented Technology Research Advancement Institution, NARO) (S.S.), and by a Grant-in-Aid for Scientific Research (S) (26220201) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (S.S.).