INHIBITION OF GLUTAMATE-INDUCED INTENSIFICATION OF FREE-RADICAL REACTIONS BY GANGLIOSIDES - POSSIBLE ROLE IN THEIR PROTECTIVE EFFECT IN RATCEREBELLAR GRANULE CELLS AND BRAIN SYNAPTOSOMES

The neurotoxic effect of exposure of rat cerebellar granule cells to g lutamate (100 mu M) is to a large extent prevented by incubation of ne urons nor only with micromolar, but even with nanomolar concentrations of gangliosides GM1, GD1b, and GT1b. GM1 was also shown to decrease s ignificantly the percent of dead neurons in culture after induction of lipid peroxidation. Exposure to glutamate was found to cause a signif icant decrease of the activity of Na+, K+-ATP-ase in rat brain cortex synaptosomes, but superoxide dismutase, alpha-tocopherol, or 10-100 nM GM1 practically prevented its action. Other data showing the ability of gangliosides to inhibit the intensification of free radical reactio ns by glutamate (based on the estimation of methemoglobin formation, S H group content, etc.) have been obtained. The results suggest that ga ngliosides are able to decrease the glutamate-induced activation of fr ee radical reactions in nerve cells. This effect appears to contribute to their protective action against glutamate neurotoxicity.