Detection of Chlamydia Muridarum Antigen and AD-Like Pathology in the Brain Tissue of Intranasally Infected BALB/c Mice

Date of Award

8-2013

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

C S Little, PhD

Second Advisor

Denah M Appelt, PhD

Third Advisor

Farzaneh Daghigh, PhD

Fourth Advisor

Marcus Bell, PhD

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease which as of 2011 affected one in eight Americans. The disease is characterized by the accumulation of beta amyloid plaques and neurofibrillary tangles in brain tissue that are believed to induce neuronal cell death. 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 can possibly induce AD-like pathology in mouse brain tissue (39). This study asks the question of whether induction of AD pathology is a feature exclusive to infection with Chlamydia pneumoniae or is common to other strains of Chlamydia. In this study nontransgenic BALB/c mice were intranasallay inoculated with Chlamydia muridarum, a mouse adapted respiratory isolate of Chlamydia trachomatis. During this study, in vivo passaged Chlamydia muridarum and stock Chlamydia muridarum were utilized. Mouse brain tissue was examined at the 60 day time point post infection for chlamydia specific labeling and amyloid pathology using immunohistochemistry techniques and visualized by brightfield microscopy. The goal of this study was to determine whether Chlamydia muridarum could establish infection in the mouse brain tissue following intranasal inoculation and induce amyloid pathology. Based on data collected from the previous mouse model with Chlamydia pneumoniae we hypothesized that intranasal infection with Chlamydia muridarum could also induce AD-like pathology in the brains ofBALB/c mice. Analysis of the data at the 2 month time point indicated varying degrees chlamydia and amyloid pathology for both the in vivo passaged Chlamydia muridarum and the stock Chlamydia muridarum. The in vivo passage Chlamydia muridarum had a greater difference in both chlamydia specific labeling and amyloid deposition between the titer negative controls and titer positive experimentals, with a 2.18 fold increase in chlamydia labeling and a 9.33 fold increase in amyloid labeling than did the stock Chlamydia muridarum, which only showed 4.16 amyloid labeling between the two groups. The data indicated that intranasal infection with Chlamydia muridarum can induce AD-like pathology in the brains of BALB/c mice. However, the data suggested that the degree of pathology induced following infection was dependent on the isolate of the organism introduced. In addition, the amount of chlamydia and amyloid immunoreactivity observed following intranasal inoculation with Chlamydia muridarum was not as great as labeling observed in past research with Chlamydia pneumoniae, which indicated that infection with this organism was not as great of a stimulus for developing AD-like pathology as was infection with Chlamydia pneumoniae.

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