Developmental lead exposure and the exacerbation of Alzheimer's pathology: an immunological analysis

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dc.contributor.advisorDeWitt, Jamie C.en_US
dc.contributor.authorVonderembse, Annalise Noelleen_US
dc.contributor.departmentBiomedical Sciencesen_US
dc.date.accessioned2014-08-28T15:05:34Z
dc.date.available2017-02-07T22:22:34Z
dc.date.issued2014en_US
dc.description.abstractEarly 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
dc.description.degreeM.S.en_US
dc.format.extent72 p.en_US
dc.format.mediumdissertations, academicen_US
dc.identifier.urihttp://hdl.handle.net/10342/4565
dc.language.isoen_US
dc.publisherEast Carolina Universityen_US
dc.subjectToxicologyen_US
dc.subjectNeuroscienceen_US
dc.subjectDevelopmental biologyen_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectDevelopmental immunotoxicologyen_US
dc.subjectMicrogliaen_US
dc.subjectNeurotoxicologyen_US
dc.subjectBiology, Neuroscience
dc.subject.meshAlzheimer Disease--pathology
dc.subject.meshDisease Progression
dc.subject.meshAmyloid beta-Protein Precursor--metabolism
dc.subject.meshPlaque, Amyloid--pathology
dc.subject.meshLead--toxicity
dc.titleDevelopmental lead exposure and the exacerbation of Alzheimer's pathology: an immunological analysisen_US
dc.typeMaster's Thesisen_US

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