Advisor | DeWitt, Jamie C. | en_US |
Author | Vonderembse, Annalise Noelle | en_US |
Date Accessioned | 2014-08-28T15:05:34Z | |
Date Available | 2017-02-07T22:22:34Z | |
Date of Issue | 2014 | en_US |
Identifier (URI) | http://hdl.handle.net/10342/4565 | |
Description | Early neuroimmune dysfunction may play a driving role in the etiopathology of Alzheimer's disease (AD), stemming from the hypothesis that many late-stage adult diseases have an early-life basis. Here we explore whether exposure to a known neuroimmunotoxicant during a period of developmental susceptibility in the central nervous system (CNS) parenchyma exacerbates the pathologies in an AD prone triple transgenic mouse model (3xTgAD). This "double-hit" research design is optimal for modeling the high variability in AD due to detrimental exogenous influences, rather than the minority of AD cases that have a well-defined genetic origin and regular neurodegenerative progression. We gavaged triple transgenic mice with lead acetate from postnatal day 5-15, a critical developmental window for microglia, immune cells of the CNS that are thought to play a major role in shaping the CNS. We then analyzed microglial phenotype and colocalization with amyloid-beta, the protein associated with AD senile plaques, to appropriately detect the change in pathological severity due to the intimate correlation of microglia with amyloid-beta plaques. Our data indicate early exposure to a neurotoxicant increases the number of activated microglia with age, which we hypothesize is due to either degradation of homeostatic inhibitory signaling pathways associated with early onset synaptic degeneration or over-burdened microglial phagocytic load. Furthmore, microglial activation states differed between genders and fluctuated with age, suggesting a sex-specific component to AD pathology and potential correlation of neurodegenerative diseases with hormone receptors in the sexual differentiation of the developing brain. | en_US |
Extent | 72 p. | en_US |
Format Medium | dissertations, academic | en_US |
Language | | en_US |
Publisher | East Carolina University | en_US |
Subject | Toxicology | en_US |
Subject | Neuroscience | en_US |
Subject | Developmental biology | en_US |
Subject | Alzheimer's disease | en_US |
Subject | Developmental immunotoxicology | en_US |
Subject | Microglia | en_US |
Subject | Neurotoxicology | en_US |
Subject | Biology, Neuroscience | |
Medical Subject Headings | Alzheimer Disease--pathology | |
Medical Subject Headings | Disease Progression | |
Medical Subject Headings | Amyloid beta-Protein Precursor--metabolism | |
Medical Subject Headings | Plaque, Amyloid--pathology | |
Medical Subject Headings | Lead--toxicity | |
Title | Developmental lead exposure and the exacerbation of Alzheimer's
pathology: an immunological analysis | en_US |
Type | Master's Thesis | en_US |
Department | Biomedical Sciences | en_US |
Degree | M.S. | en_US |