Date of Award

8-2011

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

C. Scott Little, PhD

Second Advisor

Marina D'Angelo, PhD

Third Advisor

Brian J. Balin, PhD

Fourth Advisor

Denah M. Appelt, PhD

Fifth Advisor

Marcus Bell, PhD

Abstract

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder and the most common form of dementia. The pathology in the central nervous system (CNS) impairs memory and cognition, hindering the capabilities and the quality of life of the individual. This project continues studying the role of infection and Alzheimer’s disease and contributes to the overall understanding of the possible causes of this disease. In this study, BALB/c mice were infected, via direct intracranial injection, with a respiratory isolate (AR-39) of Chlamydia pneumoniae. Their brains were analyzed at 7 and 14 days post-infection, using immunohistochemistry, for the presence of C. pneumoniae, amyloid deposits and activated glial cells. The goal of this project was to measure the location and degree of C. pneumoniae burden, amyloid deposition and glial cell activation in the CNS following direct intracranial injection and to compare this data with results obtained from previous studies in this laboratory. We hypothesized that C. pneumoniae antigen and activated inflammatory cells will be observed in the infected mouse brains following direct intracranial injection and Aβ deposition will be observed in areas where inflammation occurs. C. pneumoniae, amyloid deposits and activated glial cells were detected in the brains following direct intracranial infection with C. pneumoniae. At 7 days post-infection the average number of C. pneumoniae-specific immunoreactive sites was 68 ± 51.06 for the infected mice and, at 14 days post-infection, the average was 60 ± 43.79 for the infected mice. Within 0.84 mm of Bregma, the location of the injection, 166 of 203 total C. pneumoniae-specific immunoreactive sites (82%) and 26 of 27 (96%) total amyloid deposits were detected at 7 days post-infection. At 14 days post-infection, 126 of 179 total C. pneumoniae-specific immunoreactive sites (70%) and 13 of 32 (41%) total amyloid deposits were detected (within 0.84 mm of Bregma). From 7 to 14 days post-infection the C. pneumoniae and amyloid deposits located near the injection site spread distally from this location to other regions of the brain. These data confirm that C. pneumoniae is capable of establishing an infection in the CNS. Although deposits were observed, the lack of a substantial amount of amyloid deposits suggested that the generation of deposits may require longer than 14 days following C. pneumoniae infection. As early as 7 days post-infection, inflammation is observed in response to the presence of C. pneumoniae and/or soluble amyloid in the CNS and the contribution of both infection with C. pneumoniae and the presence of soluble amyloid elicit the inflammatory response that presumably precedes and contributes to amyloid deposition.

Download

Share

COinS