Abstract
Exercise during the inactive period can entrain locomotor activity and peripheral circadian clock rhythm in mice; however, mechanisms underlying this entrainment are yet to be elucidated. Here, we showed that the bioluminescence rhythm of peripheral clocks in PER2::LUC mice was strongly entrained by forced treadmill and forced wheel-running exercise rather than by voluntary wheel-running exercise at middle time during the inactivity period. Exercise-induced entrainment was accompanied by increased levels of serum corticosterone and norepinephrine in peripheral tissues, similar to the physical stress-induced response. Adrenalectomy with norepinephrine receptor blockers completely blocked the treadmill exercise-induced entrainment. The entrainment of the peripheral clock by exercise is independent of the suprachiasmatic nucleus clock, the main oscillator in mammals. The present results suggest that the response of forced exercise, but not voluntary exercise, may be similar to that of stress, and possesses the entrainment ability of peripheral clocks through the activation of the adrenal gland and the sympathetic nervous system.
Highlights
Exercise during the inactive period can entrain locomotor activity and peripheral circadian clock rhythm in mice; mechanisms underlying this entrainment are yet to be elucidated
Photic signals induce Per[1] expression through the activation of second messenger cascades, including ERK, PKA, and Ca2+/calmodulin-dependent protein kinase II (CaMKII), which leads to the transcriptional activation of Per[1] genes via the activation of cAMP response elements in their promoters[15,16,17]
To check whether our experimental system concurs with previous reports, mice were forced to exercise during the inactivity period
Summary
Exercise during the inactive period can entrain locomotor activity and peripheral circadian clock rhythm in mice; mechanisms underlying this entrainment are yet to be elucidated. Non-photic stimuli induced by both, novel wheel confinement and benzodiazepine drugs, can suppress the expression of Per[1] and Per[2] mRNA in the SCN. This can, at times, result in a behavioral phase shift[18,19]. The mechanisms of entrainment of the peripheral clock by scheduled exercise are not well understood
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