Effects of Corticosterone and Stress on Cry1 Expression in the Prefrontal Cortex of Male Rats, and Sex Differences in Stress-induced Cry1 Expression in the Hypothalamic Suprachiasmatic and Paraventricular Nuclei of Male and Female Rats

摘要

Promising evidence suggests that impaired circadian rhythms can lead to various mood disorders. Circadian rhythms are regulated by a master clock, the hypothalamic superchiasmatic nucleus (SCN), and its downstream circadian oscillators. Core clock genes compose the circadian clock through a system of feedback loops. A variety of inputs can modulate clock gene expression, such as glucocorticoid hormones, feeding cycles, temperature, and stress. In this study, I investigated the effects of acute stress on the expression of the core clock gene, Cry1, in the SCN, hypothalamic paraventricular nucleus (PVN), and prefrontal cortex (PFC) of rats maintained on a 12h/12h light-dark cycle. Stress has been shown to induce clock gene expression in various cell lines and tissues. In broad strokes the mechanism of stress induced clock gene expression is unknown. I hypothesized that glucocorticoid response elements (GRE’s) may play a role in stress induced clock gene expression. When bound by the glucocorticoid hormone-glucocorticoid receptor dimer, GRE’s promote transcription of genes. It has been shown that certain clock genes have GRE’s in their promoter regions. Based on this, I presumed that acute stress could increase clock gene expression in brain regions containing a high density of GR’s, if a functional GRE is present in the promoter region of the clock gene. Furthermore, I examined if there was a time of day effect of Cry1 mRNA in all three regions of interest, since clock gene expression is variable throughout a 24-hour period. I also examined whether there was a sex effect in the SCN and PVN, since there are gender differences in the magnitude of the CORT response to acute stress.