Undergraduate Honors Theses

Thesis Defended

Fall 2013

Document Type

Thesis

Department

Psychology & Neuroscience

First Advisor

Robert Spencer

Abstract

This thesis explores the role of glucocorticoids in entraining the rhythmicity of clock gene expression in components of the hypothalamic-pituitary-adrenal (HPA) axis, specifically the paraventricular nucleus (PVN) of the hypothalamus and the anterior pituitary. Physiological and behavioral circadian rhythms rely on molecular oscillators inside cells of living organisms. Rhythmic expression of associated clock genes is dependent on the hypothalamic suprachiasmatic nucleus (SCN), which is synchronized to the light/dark cycle with an intrinsic rhythm near 24 hours. Extra-SCN brain regions and peripheral tissues in the body have been shown to have molecular clocks; interestingly, the SCN has sparse direct neural input in these regions. Previous research has indicated that glucocorticoids (CORT) are able to entrain clock gene rhythmicity in peripheral tissues, suggesting the SCN may synchronize peripheral clocks through a diurnal expression of CORT. Little work has been done to explore this possible mechanism of entrainment in the brain but has been characterized in periphery where CORT has been shown to cause a phase shift, induce, or abolish clock gene expression in tissues such as liver and kidney. This thesis characterizes clock gene expression in response to three different CORT profiles: antiphasic CORT treated, phasic CORT treated, and vehicle treated in adrenalectomized rats. We found that expression of clock genes Per1 and Per2 varied with CORT treatment in both the PVN and anterior pituitary, but also that CORT influenced genes differently in the two regions. The results suggest that CORT may have a permissive effect in the periphery, necessary for clock gene expression, but has an entraining effect in the brain. This study was an important step in understanding the role of CORT in HPA axis regulation and disruption. Such disruptions and dysregulation of the HPA have been observed in numerous conditions such as Posttraumatic Stress Disorder, Major Depressive Disorder, and sleep disorders.

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