Document Type

Thesis

Abstract

Previous studies in our laboratory have shown that dietary supplementation with antioxidants is harmful during murine infection with the protozoan parasite, Toxoplasma gondii, which causes toxoplasmosis in humans. Dietary supplementation with vitamin E and selenium was shown to increase tissue cyst number, tissue pathology, and weight loss during T. gondii infection. The goal of the present study was to determine the impact of diet on global gene expression in the brains of infected and non-infected mice and to identify the major genes that are differentially expressed, determine their function, and discover the molecular pathways in which these genes participate. Whole genome screening, a method of determining global gene expression, was performed on RNA isolated from the brains of C57BL/6 mice, utilizing Agilent Oligo Microarrays (Agilent Technologies, Inc). Comparison of the transcripts in infected and non-infected brain tissue revealed 1,688 differentially expressed genes (p<0.05) in mice maintained on the antioxidant diet. Among these genes 507 were up regulated and 71 were down regulated with 2 fold change or greater. Over 60 cytokine or cytokine-related genes showed increased expression, along with 19 up-regulated chemokine-related genes. Greater than 60% of the genes which showed elevated expression could be classified as pro-inflammatory, immune function, or cellular defense genes. In mice maintained on a diet lacking vitamin E and selenium, we observed 2,743 differentially expressed genes (p<0.05) in the brains of infected mice as compared to non-infected mice. Among these genes, 239 were up regulated and 13 genes were down regulated with 2 fold or greater change. Nine chemokine or chemokine receptor genes and over 60 cytokine or cytokine receptor genes were up regulated in this comparison. The results of this study demonstrate a correlation between the increased pathology observed in infected mice maintained on an antioxidant-supplemented diet and an intense and extensive pro-inflammatory response in brain tissue.

Disciplines

Diseases | Medical Genetics