The Effect of Resveratrol on Manganese Toxicity in Astrocytes

Date of Award

7-2012

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

Department

Basic Sciences

First Advisor

Harold Komiskey, PhD

Second Advisor

Francis Jenney, PhD

Third Advisor

Desuo Wang, PhD

Abstract

Manganese (Mn) is an essential trace metal required for a variety of normal physiological processes. However, accumulation of excess Mn in the brain leads to a progressive neurological syndrome referred to as manganism. In particular, collection of excess Mn in glial cells called astrocytes is of significant importance because of their involvement and function with memory, emotional response, navigation, and spatial orientation. These cells possess a high capacity for Mn uptake and are thus more susceptible to Mn toxicity than other neural tissue. Resveratrol, a polyphenol found in grapes, is believed to have therapeutic effects against such toxic insults. In the present investigation, we employed primary rat hippocampal astrocytes to investigate the molecular changes in glial fibrillary acidic protein (GF AP) release as a measure of response to acute Mn exposure. Resveratrol was studied to determine its neuroprotective potential against acute Mn exposure. The astrocytes were treated with various concentrations ofMn sulfate (lOO/lM, 300/lM, and 600/lM) and/or resveratrol (3/lM, 10/lM, and 30/lM) and examined for dose-related changes in soluble GF AP release using an enzyme-linked immunosorbent assay (ELISA). Though it is statistically inconclusive whether Mn causes an increase in soluble GF AP or whether resveratrol alone causes a decrease in soluble GF AP, data trends suggest a potential neuroprotective ability of resveratrol at 30/lM that should be investigated further.

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