Date of Award
2010-01-01
Degree Name
Doctor of Philosophy
Department
Biological Sciences
Advisor(s)
Louis N. Irwin
Second Advisor
Donna M. Byers
Abstract
Gangliosides have been implicated in multiple pathologies affecting the central nervous system (CNS) and recent research has implicated them in playing an active role in the pathogenesis of multiple sclerosis. Empirical studies and theoretical considerations have suggested the possibility of interactions between gangliosides, like GD3, and pro-inflammatory cytokines present in the nervous system. This study sought to investigate the possibility that either individual gangliosides acting alone or complexed with other species interact with the known immune response factor TNF&alpha to initiate or facilitate cell death in the CNS. I examined the cellular viability and gene expression in primary brain cell cultures treated with either GD3, GD1b, or TNF&alpha to observe relative changes that would provide evidence for a possible pathway involved in this form of cell death. I found that both GD3 and GD1b, but not TNF&alpha led to up-regulation of gene expression for macrophage inflammatory protein 3 (MIP3A) and interleukin-1 receptor 1 (IL1R1), but down-regulation of fibroblast growth factor 13 (FGF13). The gene expression of the FGF receptor activating protein 1 (FRAG1) and interleukin-3 receptor alpha (IL3RA) was down-regulated by GD3 and GD1b for IL3RA, but only GD3 caused a down-regulation in FRAG1, while TNF&alpha caused an up-regulation in the expression of both genes. All three treatments resulted in up-regulation of the gene for chemokine ligand 2 (CCL2). TNF&alpha was also found to increase expression of the gene for N-acetyl-galactosaminyl transferase (GNT), a key enzyme in the synthesis of more complex gangliosides. These findings support the view that a pro-inflammatory stimulus, like TNF&alpha , activates biosynthesis of gangliosides, which subsequently breaks down to forms not normally expressed in differentiated cells, like GD3, which then lead to or modulate cell death.
Language
en
Provenance
Received from ProQuest
Copyright Date
2010
File Size
106 pages
File Format
application/pdf
Rights Holder
John Charles Gorbet
Recommended Citation
Gorbet, John Charles, "Ganglioside-Cytokine Interaction in the Induction of Primary Brain Cell Death" (2010). Open Access Theses & Dissertations. 2691.
https://scholarworks.utep.edu/open_etd/2691