Abstract

Introduction

Astrocytes and Oligodendrocytes

Other Neural Cell Types

Future Directions

References

Discussion
Board

Oligodendroglia and neurons produce more peroxides than astrocytes because of their higher rate of oxidative metabolism. This makes them more susceptible to perturbations since peroxides can be converted to powerful oxidants. We have demonstrated that cultured immature oligodendrocytes are more susceptible to perturbations such as elevated temperature and hypoxia than astrocytes. This susceptibility is due, in part, to: i) higher iron content thus enabling conversion of peroxides to strong oxidants, ii) lower activities of glutathione peroxidase, and iii) lower reduced-glutathione (GSH). The lower GSH is related to lower activities of of glutathione reductase and glutathione synthase. Oligodendroglia have a more than 10-fold decrease in activities of other phase II enzymes such as quinone reductase. When oligodendroglial GSH content was raised, their ability to withstand oxidative stress was markedly increased. Neurons appear to be susceptible to oxidative stress for similar reasons. We have further shown that the observations in cultured cells have relevance to cells in vivo since immature oligodendroglia in the developing brain are preferentially affected by severe oxidative insults. We suggest that developing therapeutic approaches that result in small increases in neural GPx and/or GSH could minimize damage normally associated with a variety of neurodegenerative diseases.

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Presentation Number SAeftekharpour0439
Keywords: glia, glutathione, neuron, oxidative stress, CNS