Date of Award

Spring 1-1-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Robert L. Spencer

Second Advisor

Serge Campeau

Third Advisor

Ryan K. Bachtell

Fourth Advisor

Sona Dimidjian

Fifth Advisor

Pei-San Tsai

Abstract

In order to optimize its survival, an organism needs to be synchronized to its environment. Thus, properly entrained circadian rhythms are critical for normal health and behavior, as many mood disorders are associated with disrupted circadian rhythms. Circadian rhythms are controlled by the oscillating expression of core clock genes, including Per1, Per2, and Bmal1. While this molecular clock is well-established in the body’s master clock, the hypothalamic suprachiasmatic nucleus (SCN), there is limited characterization of oscillating molecular clocks in extra-SCN brain regions. Furthermore, there are sex differences in circadian rhythms. Thus, the first study characterized the ubiquitous existence of oscillating molecular clocks (Per1, Per2, and Bmal1 mRNA; in situ hybridization) in the prefrontal cortex, amygdala, hippocampus, and the hypothalamic paraventricular nucleus (PVN) in male and female rats. It has been proposed that the SCN is able to entrain these extra-SCN molecular clocks through the diurnal rhythm of glucocorticoids (CORT). Adrenalectomy disrupts clock gene expression in the PFC. If a timely peak in diurnal CORT is necessary for normal clock gene rhythm, then untimely stress-induced peaks in CORT may disrupt clock gene expression. There are sex differences in stress. Thus, it was examined if 30 minutes of acute restraint stress could alter clock gene expression in the PFC and PVN of male and female rats, whether this effect was dependent on the presence of CORT, and if this effect could be modulated by estradiol in female rats. Acute stress selectively and rapidly induces Per1 mRNA (in situ hybridization) in the PVN and PFC of male and female rats. There were no sex differences, despite greater stress-induced CORT in females. Furthermore, stress-induced Per1 mRNA was largely independent of CORT in both males and females, as adrenalectomy had limited effects. Additionally, in females, estradiol had no effect, either acutely or permissively, on stress-induced Per1 mRNA. The selectivity of Per1 induction suggests that Per1 may act as an incident detector for the molecular clock to salient cues in the environment in order for the organism to adapt to changes in its environment.

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