Undergraduate Honors Thesis


The Effect of Stress, Time of Day and Adrenal Hormones on Bmal1, Per2 and C-Fos Expression in the Rat Hippocampus and Amygdala Public Deposited

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  • The term circadian rhythm refers to the behavioral and physiological changes an organism exhibits during an approximately 24-hour period. Plants, animals and fungi all maintain circadian rhythms, by part, with a molecular clock system. The molecular clock consists of a positive and negative feedback loop that alter gene transcription and translation. BMAL1 and CLOCK make up the positive transcription arm that stimulates the production of two classes of genes, period (Per 1-3) and cryptochrome (Cry 1-2). PER and Cry protein make up the negative feedback loop of the molecular clock and inhibit their own transcription in the nucleus. The molecular clock system must be reset, or entrained, on a daily basis. The steroid hormone corticosterone (CORT) is thought to be the hormonal signal that entrains peripheral molecular clock systems. CORT is released when stressors activate the hypothalamic pituitary adrenal (HPA) axis. This study examines the role stress, endogenous CORT and time of day play in the expression of Per2, Bmal1 and c-Fos in rat hippocampus and amygdala. C-fos was chosen as a positive control to ensure that cells were generally responsive to stress. Acute restraint stress was used to model mild psychological stress in rats. Endogenous CORT was manipulated using sham and adrenalectomy (ADX) surgeries. Tissue samples were taken at ZT4 and ZT16 and analyzed via insitu hybridization to measure relative mRNA levels. There was a robust stress effect seen with c-Fos expression in all brain regions examined except for the superior portion of the dentate gyrus. Per2 shows a significant time of day effect in CA1, CA3 and BLA. CEA showed an interesting time of day by endogenous CORT status interaction. These data show that Per2 and Bmal1 are not rapidly induced by stress like the clock gene Per1. Future studies should analyze data at supplementary time points and alter the type of stressor utilized to see if those variables effects Per2 and Bmal1 expression.
Date Awarded
  • 2017-01-01
Academic Affiliation
Granting Institution
Last Modified
  • 2019-12-02
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