Impacts of Perinatal High Fat Diet and Prenatal Stress Exposure on the Programming of the Hypothalamic-Pituitary-Adrenal Axis and Anxiety-like Behaviour in Rats
Year: 2019
Type: dissertation
Abstract: The maternal environment has a profound effect on the development of offspring, including responses to stress mediated by the hypothalamic-pituitary-adrenal (HPA) axis. Maternal diet and stress are two environmental factors that program the HPA axis in a manner that persists throughout adulthood, however there are no reports of their joint effect on the development of the HPA axis and anxiety-like behaviour. The objective of this thesis was to examine the effects of maternal obesity in the form of high fat diet (HFD) consumption and maternal stress in the form of exposure to chronic variable stress (CVS) on stress-related behavioural, endocrine, and molecular measures in neonatal and adult offspring in rats. I hypothesized that combined effects perinatal HFD and prenatal CVS would have synergistic effects on programming of stress-related phenotypes. I observed strong main effects of perinatal HFD on offspring anxiety-like behaviours and HPA axis physiological responses. Interestingly, CVS normalized the effects of perinatal HFD on anxiety-like behaviour in adult female offspring and physiological stress response in neonate offspring. I also characterized maternal physiological and behavioural responses to HFD consumption and CVS exposure and found increased sensitivity to CVS in HFD dams. Further, examining the interaction between the dam and neonatal offspring using maternal behaviour and pup ultrasonic vocalization (USVs) characteristics, I found impaired pup retrieval in HFD dams and altered USV characteristics in HFD neonates. Finally, due to the main effects of perinatal HFD on behavioural and physiological phenotype, I examined differential effects of maternal HFD consumption on offspring gene expression and the epigenome in brain regions that regulate the HPA axis. I observed increased Crh expression in the PVN and decreased Nr3c1 expression in the ventral hippocampus in neonates along with differential methylation of genes involved in neuronal development in the amygdala. In adulthood, HFD induced differential DNA methylation in genes involved in protein phosphorylation, specifically GTPase related genes. Findings in this thesis provides several avenues for future studies in both mother and offspring, including possible intervention studies targeting dam-pup interaction and molecular mechanism underlying the programming effects of perinatal HFD in offspring.
Source: TSpace (University of Toronto)
Author: Sameera Abuaish
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3153296043