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035 a| (Sirsi) o891139852;

035 a| (OCoLC)891139852;

040 a| EREe| rdac| EREd| UtOrBLW;

049 a| EREE;

100 1 a| vonderEmbse, Annalise Noelle,e| author.?| UNAUTHORIZED;

245 10 a| Developmental lead exposure and the exacerbation of Alzheimer's pathology: an immunological analysis /c| by Annalise Noelle vonderEmbse.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2014.;

300 a| 72 pages :b| illustrations (some color);

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 0.98Mb2| rda;

490 1 a| ECU Brody School of Medicine thesis;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| M.S.c| East Carolina Universityd| 2014.;

500 a| Presented to the faculty of the Department of Pharmacology and Toxicology.;

500 a| Advisor: Jamie C. DeWitt.;

500 a| Title from PDF t.p. (viewed September 23, 2014).;

520 3 a| 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.;

504 a| Includes bibliographical references.;

650 2 a| Alzheimer Diseasex| pathology.=| ^A1201837;

650 2 a| Disease Progression.=| ^A929952;

650 2 a| Amyloid beta-Protein Precursorx| metabolism.=| ^A1260958;

650 2 a| Plaque, Amyloidx| pathology.=| ^A1261002;

650 2 a| Leadx| toxicity.=| ^A923859;

653 a| Toxicology;

653 a| Neurosciences;

653 a| Developmental biology;

700 1 a| DeWitt, Jamie C.,e| degree supervisor.=| ^A1261265;

710 2 a| Brody School of Medicine.b| Office of Research and Graduate Studies.b| Biomedical Sciences.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine thesis.=| ^A964744;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/4565;

949 a| Click on web addressw| ASISh| JOYNER101o| jdjr;

949 a| Click on web addressw| ASISh| HSL111o| jdjr;

994 a| C0b| ERE;

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596 a| 1 4;

998 a| 3514292;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 3514292-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 9/23/2014x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 3514292-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 9/23/2014x| ETDz| HERESOURCE;

Developmental lead exposure and the exacerbation of Alzheimer's pathology: an immunological analysis / by Annalise Noelle vonderEmbse.

Author/creator	vonderEmbse, Annalise Noelle author.
Other author	DeWitt, Jamie C., degree supervisor.
Other author	Brody School of Medicine. Office of Research and Graduate Studies. Biomedical Sciences.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2014.
Description	72 pages : illustrations (some color)
Supplemental Content	Access via ScholarShip
Subjects	Alzheimer Disease--pathology. Disease Progression. Amyloid beta-Protein Precursor--metabolism. Plaque, Amyloid--pathology. Lead--toxicity.

Series	ECU Brody School of Medicine thesis ECU Brody School of Medicine thesis. ^A964744
Summary	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.
General note	Presented to the faculty of the Department of Pharmacology and Toxicology.
General note	Advisor: Jamie C. DeWitt.
General note	Title from PDF t.p. (viewed September 23, 2014).
Dissertation note	M.S. East Carolina University 2014.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Developmental lead exposure and the exacerbation of Alzheimer's pathology: an immunological analysis / by Annalise Noelle vonderEmbse.

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