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

Mayo Kamagata, Yuko Ikeda, Hiroyuki Sasaki, Yuta Hattori, Shinnosuke Yasuda, Shiho Iwami, Miku Tsubosaka, Ryosuke Ishikawa, Ai Todoh, Konomi Tamura, Yu Tahara, Shigenobu Shibata*

*この研究の対応する著者

研究成果: Article査読

13 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1067-1082
ページ数16
ジャーナルChronobiology International
34
8
DOI
出版ステータスPublished - 2017 9 14

ASJC Scopus subject areas

  • 生理学
  • 生理学(医学)

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