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|Title:||Effects of prenatal stress on circadian rhythms and metabolism in adult rat offspring|
|Keywords:||Circadian rhythms;fetal programming;metabolism;hypertension;spontaneously hypertensive rat (SHR);dexamethasone|
|Abstract:||Circadian clocks developed in organisms as a way of estimating the time of day and control many vital aspects of physiology from the sleep-wake cycle to metabolism. The circadian clock operates through transcriptional-translational feedback loops. The normal circadian signaling relies on a ‘master clock’, located in the suprachiasmatic nucleus (SCN), which synchronizes peripheral oscillators. Here, glucocorticoid receptor (GR) signaling has the ability to reset the phase of peripheral clocks. It has been shown that maternal exposure to the stress hormone, glucocorticoids (GCs), can lead to modification of hypothalamic-pituitaryadrenal (HPA) function and impact stress-related behaviours and a hypertensive state via GR activation. We previously demonstrated altered circadian rhythm signaling in the adrenal glands of offspring exposed to the synthetic glucocorticoid, dexamethasone (Dex). Results from the current study show that prenatal exposure to Dex, affects circadian rhythm gene expression in a tissue and sex specific manner in molecular oscillators of the amygdala, hippocampus, paraventricular nucleus and prefrontal cortex as well as the main oscillator in the SCN. Results also show that spontaneously hypertensive rats (SHRs) exhibited dysregulated circadian rhythms in these same brain regions compared with normotensive Wistar-Kyoto rats (WKYs), although the pattern of dysregulation was markedly different from that seen in the Dex model. Metabolomic and gene expression results in the livers of GCexposed offspring revealed sex specific metabolic profiles with females displaying increased lipid and glutathione metabolism, increased triglyceride concentration and decreased purine metabolism while males saw increased purine metabolism and evidence of an adaptation for increased lipid metabolism.|
|Appears in Collections:||Biology - Master's Theses|
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|Alyssa Murray - Master's Thesis.pdf||1.32 MB||Adobe PDF|
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