ASTROCYTE-ENHANCED NEURONAL SURVIVAL IS MEDIATED BY SCAVENGING OF EXTRACELLULAR REACTIVE OXYGEN SPECIES

The survival of cultured neurons is promoted by the presence of antiox idants or astrocytes. This indicates that extracellular reactive oxyge n species (ROS) impair neuronal survival and suggests that astrocytes exert their survival-enhancing effect through inactivation of these to xicants. However, to our knowledge, data supporting this hypothesis ar e lacking. Previously, we showed that loss of the antioxidant glutathi one abolishes the neuronal survival-stimulating action of astrocytes i n cocultures, consisting of rat striatal astrocytes and mesencephalic, dopaminergic neurons. Using uptake of [H-3]dopamine as marker of neur onal survival, we presently investigated whether this effect of glutat hione depletion is mediated by extracellular ROS. For this purpose, we incubated glutathione-depleted cocultures with superoxide dismutase, catalase or both. Whereas superoxide dismutase had no effect and catal ase only partially protected, addition of the enzymes together complet ely prevented the impairment of neuronal survival caused by glutathion e loss. No change in neuronal survival occurred upon exposure of contr ol cocultures to superoxide dismutase and/or catalase. These data stro ngly implicate scavenging of extracellular ROS in astrocyte-stimulated neuronal survival and moreover suggest a crucial role for glutathione in this process. (C) 1998 Elsevier Science Inc.