The main aim of this thesis was to assess if early deprivation (ED) and glucocorticoid (GC) treatment exert long-term effects on the volume of the brain regions implicated in responses to stress, and if it associates with alterations in the distribution and structure of astroglia, which are known to support brain plasticity. This study also investigated the effects of prenatal dexamethasone (Dex) treatment on selected brain receptors, namely the oxytocin and 5-HT1A receptors, as they are implicated in the regulation of responses to stress. In addition, in vitro effects of Dex on neural stem cells were studied, in order to explore the drug effects on cell proliferation and differentiation, and on glial cell markers. Unbiased stereological estimation was employed to determine the regional brain volume, astroglial morphology and total cell count. Peripheral quantitative computed tomography (pQCT) technique was used to quantify total brain volume. Autoradiography technique was employed to visualise and analyse oxytocin and 5HT-1A serotonin receptor binding using selective radioactive ligands. The results of the present study demonstrate that both ED and prenatal Dex exposure leads to long-term effects on hippocampal remodelling with volume losses and impoverished astroglial morphology in the form of reduced primary process length. The observed deterioration in astroglial morphology adds further evidence that astrocytic changes contribute to hippocampal volume losses, a phenomenon that deserves more research in the context of effects of corticosteroid overload and stress-related pathologies. The present results also demonstrate that prenatal Dex induces long-term effects at the level of central neuroregulatory processes. Thus significant region- and sex-dependent reductions or increases in the oxytocin and 5-HT1A receptor binding were observed. The in vitro study has shown that Dex affects both proliferation and differentiation of GFAP positive NSCs with no toxic effects as such. Overall, both early postnatal or prenatal manipulations that increase levels of stress and/or glucocorticoids as the chemical mediators of stress, lead to a long-term maladaptive brain remodelling with losses in the hippocampal volume, impoverishment of hippocampal astroglial morphology and changes in the properties of central regulatory receptors in the brain areas involved in the reaction to stress.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:580550 |
| Date | January 2013 |
| Creators | Shende, Vishvesh H. |
| Contributors | Opacka Juffry, Jolanta ; Belai, Abebech |
| Publisher | University of Roehampton |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://pure.roehampton.ac.uk/portal/en/studentthesis/“long-term-effects-of-prenatal-and-early-postnatal-environment-on-brain-remodelling(e6d0d93b-db49-4632-a3a9-9ff4e7b623da).html |
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