Identifier

etd-01152007-182354

Degree

Master of Science (MS)

Department

Veterinary Medical Sciences - Pathobiological Sciences

Document Type

Thesis

Abstract

Microglia/macrophage activation has been associated with the pathogenesis of various neurological diseases including human immunodeficiency virus encephalitis, transmissible spongiform encephalitis, and Alzheimer's disease (AD). In vitro studies have indicated a role for TNFα in activating these cells which leads to their migration, proliferation, and secretion of proinflammatory cytokines and chemokines that may potentially damage brain tissue. In the current study, we analyzed the phenotype of microglia and macrophages enriched from wild type and TNFα deficient mice infected with a neurovirulent murine retrovirus. Although TNF receptors CD120a and CD120b were expressed on both microglia and macrophage population, unaltered by either retrovirus infection or TNFα deficiency. To determine if hindering microglia/macrophage activation and TNFα expression during an established viral infection would impede the development of neurological disease, we treated mice with minocycline which has been reported to inhibit both microglia activation and TNFα production. Despite the decreased expression of certain genes involved in TNF signaling and microglia/macrophage activation, there was no delay in onset of neurological disease between PBS and minocycline treated EC infected mice. mRNA expression for accessory molecules involved in the TNF Superfamily signaling was significantly reduced with minocycline treatment. Understanding how to better manipulate these pathways could lead to ways to decrease the severity of neurological disease in not solely this model but others in which they has been directly linked to pathogenesis.

Date

2007

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Karin E Peterson

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