Author

Johnny Barr

Document Type

Thesis

Date of Award

5-2003

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Biology

First Advisor

Govindarajan T. Ramesh

Abstract

Manganese (Mn), an element that in traces amounts is critical for normal cell function and health, but at high concentrations is causes severe neurodegenerative disease. Mn is a gasoline additive in the United States and thus most chronic exposure to Mn occurs through the environment. Individuals surviving a severe Mn-intoxication often develop neuromotor degenerative conditions, a delayed Parkinson-like disease. The cellular and molecular mechanisms involved in Mn toxicity are poorly understood. The main goal of this project is to elucidate the mechanisms underlying the effects of Mn on mesenceplalic cell culture model system. We used a novel immortalized rat mesenceplalic (lRB3AN27) cell line that has unique advantages as a model to study Mn induced neurotoxicity. In this study it was shown that exposure of mescencephalic cell to Mn produces alterations in oxidative stress mediated signaling mechanism. Mn exposure of these cells also decreased cell viability dose-dependently and increased intracellular 1 2 generation of reactive oxygen species with decreased glutathione levels. In addition, DNA fragmentation was observed with increase concentrations of Mn. These findings clearly suggest that alterations in oxidative stress during Mn exposure may have a significant cytotoxic effect on neuronal function

COinS