Date of Award

2016

Degree Type

Thesis

First Advisor

C S Little, PhD

Second Advisor

Denah M Appelt, PhD

Third Advisor

Dawn Shell, PhD

Fourth Advisor

Kerin Claeson, PhD

Fifth Advisor

Marcus Bell, PhD

Abstract

Alzheimer's' Disease (AD) is a progressive neurodegenerative disease that affects millions of elderly individuals in the western world. There are two forms of AD, sporadic late-onset AD and Familial AD. The neuropathy seen in both cases of AD is the same; neurofibrillary tangles (NFTs) that are composed of modified tau protein, and neuritic senile plaques (NSPs) composed of deposited beta amyloid peptide. The objective of this study is to continue to investigate the role of infection as a possible risk factor for sporadic AD. Previous mouse models using Chlamydia pneumoniae demonstrated that intranasal inoculation with this organism induced AD-like pathology in mouse brain tissue { {17 Little,C.S.( 1) 2004;} }. Previous studies examined non-transgenic BALB/c mice that were intranasally inoculated with an in vivo passaged isolate of C. muridarum (C small Weiss) and a stock isolate of C. muridarum (mouse pneumonitis Weiss), a mouse adapted respiratory isolate of C. trachomatis. The presence of C. muridarum antigen as well as deposited beta amyloid was established at the 60-day time point. The goal of this study was to determine whether astrocyte activation would be identified within brain tissue previously verified with infection of C. muridarum and deposited beta amyloid. Based on previously observed AD-like pathology, it was hypothesized that astrocytes will respond to infection and deposited beta amyloid and become activated. At the 2 month time point, Semiquantitative, immunohistochemical and microscopic analysis revealed great variability in glial cell specific labeling in mice intrasnasally inoculated with either isolate of C. muridarum. Analysis of the stock isolate of C. muridarum revealed an approximate 3-fold increase between the titer negative group and the titer positive 1:20480 experimental group. Analysis of the in vivo passaged isolate displayed less than a 10% difference in total glial cell number between the titer negative and the titer positive 1:10240 experimental group. These data indicate that intranasal infection with C. muridarum induces glial cell activation in the brains of BALB/c mice. However these data suggest that the degree of activation is dependent on the isolate of C. muridarum introduced. The initial hypothesis proposed that glial cell burden would increase in response to chlamydia infection and amyloid pathology. However, an inverse correlation between glial cell count and amyloid deposit burden was noted in both isolates of C. muridarum, although there was a considerably greater inverse correlation between glial cell count and amyloid burden in the mouse pneumonitis Weiss stock group. In accordance with the initial hypothesis, as chlamydia antigen burden increased, glial cell counts also increased in the C small Weiss group. However, the relationship of glial cells and chlamydia antigen burden differed from the initial hypothesis for the mouse pneumonitis Weiss group. As chlamydia antigen burden increased, glial cell counts decreased. These data suggest that the in vivo passaged C small Weiss isolate is more virulent than the stock passaged mouse pneumonitis Weiss isolate of C. muridarum.

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