The role of Bax in glutamate-induced nerve cell death

The role of the Bax gene product was examined in three forms of cortical ne rve cell death in primary cultures. These include spontaneous cell death, o xidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake resulting in toxic oxidative stress, and ionotropic glutamate recept or-mediated excitotoxicity following a brief exposure to 10 muM glutamate. Primary cortical and hippocampal neuron cultures were established from embr yos of Bar -/+ x Bax -/+ matings and the embryos genotyped and assayed for cell death in the three experimental paradigms. Cell death induced by oxida tive glutamate toxicity and glutamate-mediated excitotoxicity was not alter ed in the Bax-/- homozygous knockout animals. In contrast, there was an app roximately 50% inhibition of spontaneous cell death. These results suggest that a classical Bar-dependent apoptotic pathway contributes to the spontan eous cell death that takes place when nerve cells are initially exposed to cell culture conditions. A Bax-dependent programed cell death pathway is no t, however, utilized in oxidative glutamate toxicity and NMDA receptor-medi ated excitotoxicity following a brief exposure to low concentrations of glu tamate.