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.
| Identifer | oai:union.ndltd.org:LSU/oai:etd.lsu.edu:etd-01152007-182354 |
| Date | 23 January 2007 |
| Creators | Corbin, Meryll E |
| Contributors | Karin E Peterson, K. Gus Kousoulas, Stephania A. Cormier |
| Publisher | LSU |
| Source Sets | Louisiana State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lsu.edu/docs/available/etd-01152007-182354/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached herein a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to LSU or its agents the non-exclusive license to archive and make accessible, under the conditions specified below and in appropriate University policies, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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