Edinburgh Research Archive logo

Edinburgh Research Archive

University of Edinburgh homecrest
View Item 
  •   ERA Home
  • Edinburgh Medical School
  • Edinburgh Medical School thesis and dissertation collection
  • View Item
  •   ERA Home
  • Edinburgh Medical School
  • Edinburgh Medical School thesis and dissertation collection
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Prenatal dexamethasone exposure: glucocrticoid programming of the brain

View/Open
Zeng2016.docx (2.522Mb)
Zeng2016.pdf (3.596Mb)
Date
02/07/2016
Author
Zeng, Yan
Metadata
Show full item record
Abstract
Human epidemiological studies have provided compelling evidence that prenatal environmental events are associated with significantly increased risks of developing neuropsychiatric disorders in adulthood. This phenomenon has been studied and known as ‘fetal programming of adult diseases’. According to the theory, environmental insults occurring at critical periods of pregnancy can permanently alter the structure and physiology of the developing organs, and may lead to adverse functional consequences that manifest later in life. It has been suggested that increased maternal glucocorticoids may be one common mechanism through which various environmental insults can affect on the developing fetus. Therefore, in this thesis, I studied the long-term prenatal glucocorticoid overexposure effects on the functioning of the brain and investigated possible molecular mechanisms underlying the programmed effects. By using a rat model of prenatal dexamethasone (100μg/kg per day) administered to pregnant dams during the last week of gestation, I found that prenatal dexamethasone overexposure significantly reduced birth weight in both male and female offspring. I also assessed the consequences of prenatal dexamethasone treatment on stress response and cognition in the adult male offspring by using a number of physiological and behavioural measures. Overall I found no evidence of prenatal dexamethasone treatment effect on the hypothalamic-pituitaryadrenal (HPA) axis activity and behavioural responsivities to an acute stress in adult male offspring; however, prenatal dexamethasone exposure affected hippocampus and prefrontal cortex related cognition in the adult offspring, including contextual fear conditioning and behavioural flexibility on water maze tasks. I further explored possible molecular mechanisms that underlie the behavioural phenotypes of the prenatal dexamethasone rat model, and found altered brain gene expression with possible implications in synaptic plasticity and retrotransposon activities. Collectively, my current study suggests that prenatal dexamethasone exposure induces long-term programming effects on adult behaviour, associated with altered gene expression profile of the brain in the rat offspring. These results provide further evidence that prenatal glucocorticoid exposure may affect the development of the brain and its influence may endure into adulthood.
URI
http://hdl.handle.net/1842/22809
Collections
  • Edinburgh Medical School thesis and dissertation collection

Library & University Collections HomeUniversity of Edinburgh Information Services Home
Privacy & Cookies | Takedown Policy | Accessibility | Contact
Privacy & Cookies
Takedown Policy
Accessibility
Contact
feed RSS Feeds

RSS Feed not available for this page

 

 

All of ERACommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsPublication TypeSponsorSupervisorsThis CollectionBy Issue DateAuthorsTitlesSubjectsPublication TypeSponsorSupervisors
LoginRegister

Library & University Collections HomeUniversity of Edinburgh Information Services Home
Privacy & Cookies | Takedown Policy | Accessibility | Contact
Privacy & Cookies
Takedown Policy
Accessibility
Contact
feed RSS Feeds

RSS Feed not available for this page