The Role of Exercise in Controlling Central Mediators of Circadian Rhythm

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Our overarching hypothesis is that chrono-timed exercise can restore rhythms in a misaligned central circadian clock. Despite the well-known benefits of exercise to overall health, limited studies have utilized exercise as a way to restore clock function, specifically in the SCN. Exercise can entrain peripheral clocks and elicit circadian phase-shifting effects but the underlying mechanisms are unknown. In particular, the coordinating efforts of the SCN in such exercise-induced entrainment of peripheral clocks is not fully known. It has recently been reported that mid-afternoon exercise in humans can phase-shift the peripheral molecular clock, yet more studies are needed to determine how exercise can be a chronobiological tool for alleviating circadian misalignment, specifically in the SCN. Our lab utilizes a well-published rodent model of circadian disruption. In addition, coupling my expertise of exercise science with our established model of circadian disruption uniquely qualifies our lab to study this aim. This proposal will implement a disruption of the light cycle to mimic chronic circadian disruption as seen in humans. Exercise will then be implemented to test if a normal rhythm can be restored. In this pilot study, we propose to test our central hypothesis that exercise during circadian disruption will re-align a disrupted central circadian clock through one specific aim comprised of two experiments. Our goal is to gain a better understanding of how exercise restores proper circadian function during circadian disruption. Our preliminary evidence suggests that chrono-timed exercise during circadian disruption via continual light-dark cycle phase shifts results in a pattern of Fos expression (a marker of neuronal activation) that more closely resembles undisrupted mice compared to mice that did not exercise. Here we will examine the relationship of this restored Fos pattern to markers of specific SCN input pathways that are known to be associated with exercise-induced entrainment, neuropeptide Y (NPY) and serotonin (5HT). We will also examine the molecular mediators underlying such modulation using RNA-seq, to determine whether the receptors for these pathways are upregulated.