Nerve growth factor, ganglioside and vitamin E reverse glutamate cytotoxicity in hippocampal cells

The present work showed that glutamate decreased hippocampal cell viability in a dose-dependent manner. While no significant effect was observed after cell exposure to 0.1 mM glutamate, cell incubation for 0.5 h caused a progressive decrease of cell viability, which at 5 mM concentration reached 68% as compared to controls. No further effect was observed in the presence of 10 mM glutamate. While nerve growth factor (NGF) at the dose of 0.5 ng/ml presented no effect, it significantly reduced glutamate cytotoxicity at a higher dose (1 ng/ml) increasing the cell viability to 66%. Similarly, cell viabilities in the presence of the ganglioside GM(1) (5 and 10 ng/ml) after glutamate exposure were 19 and 73%, respectively. A dose-response relationship was observed after cell incubation with vitamin E (0.5 and 1 mM) which resulted in cell viability of the order of 34 and 70%, respectively. Surprisingly, a potentiation of the effect was observed after the association of NGF (0.5 ng/ml) plus ganglioside GA(1) (5 ng/ml) or vitamin E (0.5 mM) plus ganglioside GM(1) (5 ng/ml), after pre-incubation with glutamate. In these conditions, significantly higher viabilities were demonstrated (66 and 71% for the two associations, respectively) as compared to each one of the compounds alone (NGF 0.5 ng/ml-29.5%; ganglioside GM(1) 5 ng/ml-19.4%). However, no potentiation was seen after the association of NGF plus vitamin E on glutamate pre-exposed cells. These results showed a cytoprotective effect of ganglioside GM(1), NGF and vitamin E on the glutamate-induced cytotoxicity in rat hippocampal cells. (C) 1999 Elsevier Science B.V. All rights reserved.