Developmental lead exposure and the exacerbation of Alzheimer's pathology: an immunological analysis
Author
Vonderembse, Annalise Noelle
Abstract
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.
Date
2014
Citation:
APA:
Vonderembse, Annalise Noelle.
(January 2014).
Developmental lead exposure and the exacerbation of Alzheimer's
pathology: an immunological analysis
(Master's Thesis, East Carolina University). Retrieved from the Scholarship.
(http://hdl.handle.net/10342/4565.)
MLA:
Vonderembse, Annalise Noelle.
Developmental lead exposure and the exacerbation of Alzheimer's
pathology: an immunological analysis.
Master's Thesis. East Carolina University,
January 2014. The Scholarship.
http://hdl.handle.net/10342/4565.
May 09, 2024.
Chicago:
Vonderembse, Annalise Noelle,
“Developmental lead exposure and the exacerbation of Alzheimer's
pathology: an immunological analysis”
(Master's Thesis., East Carolina University,
January 2014).
AMA:
Vonderembse, Annalise Noelle.
Developmental lead exposure and the exacerbation of Alzheimer's
pathology: an immunological analysis
[Master's Thesis]. Greenville, NC: East Carolina University;
January 2014.
Collections
Publisher
East Carolina University