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

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.

Traumatic stress and the circadian system: neurobiology, timing and treatment of posttraumatic chronodisruption

“…GCs are, thus, not just a downstream hormonal output of the circadian system, but can also influence the circadian system itself and interact with peripheral clocks towards a circadian symphony (Balsalobre, 2000;Dickmeis, 2009). Even externally applied GCs can alter circadian gene oscillation in peripheral clocks (Kamagata et al, 2017;Pezuk et al, 2012) and are able to even speed up or slow down circadian adaptation to a new extrenal nyctohemeral rhythm (Kiessling, Eichele, & Oster, 2010). GC rhythm alterations can, thus, affect the central and peripheral circadian system and vice versa (Koyanagi et al, 2006;Son et al, 2008).…”

The importance of determining circadian parameters in pharmacological studies

“…Also in 2013, Saini and colleagues were able to perform in vivo real‐time recording in the liver of awake mice (Saini et al, ). Since then, these and similar models have been used to study the effects of diseases, such as diabetes (Hou, Su, Guo, & Gong, ), and drugs, like glucocorticoids (Kamagata et al, ), on circadian rhythm fluctuations in peripheral organs. The main disadvantages of this type of approach are the need for specific and expensive equipment and the fact that it requires conditions of total darkness for bioluminescence readings.…”

Day-Night Oscillation of Atrogin1 and Timing-Dependent Preventive Effect of Weight-Bearing on Muscle Atrophy

“…Six-week-old male Kwl:ICR mice (body weight: 25.7–34.8 g) were obtained from Tokyo Laboratory Animals Science. C57BL:6 J- Clock m1Jt :J ( Clock mutant ) mice were obtained from Jackson Laboratory (RRID:IMSR_JAX:002923) and backcrossed to ICR mice in our previous report [30]. Six- to ten-week-old male wild-type (WT; body weight: 27.6–42.7 g) and Clock mutant ( Clock Δ19 ; body weight: 27.7–42.0 g) mice backcrossed to ICR mice were used.…”