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IDENTIFYING UPREGULATED MOLECULAR MEDIATORS VIA RNA-SEQUENCING IN EXERCISE-INDUCED ENTRAINMENT OF CIRCADIAN RHYTHMS

Abstract

A disrupted circadian rhythm compromises the health and well-being of individuals by inducing a series of physiological responses linked to several non-communicable diseases. This study explored how exercise during a disrupted circadian rhythm can re-entrain the misaligned central clock of the suprachiasmatic nucleus (SCN), the control center of such rhythms. Existing literature identifies that supplementation of chrono-timed exercise can induce a phase shift in peripheral clocks; however, more studies are needed to evaluate the role of exercise on the circadian alignment of the central clock. Preliminary data indicates positive exercise-induced changes in the SCN when subjects participated in chrono-timed exercise. PURPOSE: This study aimed to identify mechanisms via RNA-sequencing analysis by which chrono-timed exercise during circadian rhythm disruption can re-entrain the misaligned central clock. METHODS: This work was approved by the University of Wyoming IACUC. This study employs RNA-sequencing of n=16 male and n=16 female mice subjected to either a disrupted circadian protocol with or without chrono-exercise to identify upregulated receptors of molecular mediated pathways, specifically neuropeptide Y (NPY) and serotonin (5-HT) which have been implicated in neural pathways of activity. The animals’ brains were dissected, the SCNs were extracted (“punched”), and the tissue was sent for analysis. RESULTS: The most abundant cell types identified by RNA- sequencing were inhibitory, excitatory, astrocytes, and oligodendrocytes. Prominent upregulation of excitatory and inhibitory cell types indicated further examination. The data established a key focus on 10 genes expressed in excitatory and inhibitory cell types, marked by immense upregulation and a potential link to the circadian system. CONCLUSION: Inhibitory cell types were more robust in females who underwent disruption protocol potentially due to disruption of the circadian system. Excitatory cell types were only expressed in male exercise groups regardless of disruption. Further research is needed to establish these connections by examining six genes of interest that potentially play an important role in circadian realignment via supplementation of chrono-timed exercise. This work was supported by NIH Grant 2P20GM12131006. Master’s Student Poster Honors WINNER

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