Chronic glutamate toxicity in mouse cortical neuron culture

Abstract

Two pathways for glutamate toxicity have been described, receptor-mediated excitotoxicity andnon-receptormediatedoxidative glutamate toxicity.Here,we showthat two distinct forms of receptor-mediated primary cortical neuronal death exist, chronic and acute glutamate toxicity, and that these depend on exposure time. In vitro, neuronal sensitivity to chronic glutamate exposure increased as neuronsmatured and the initial platingmediumcontributed as well. In immature neurons, high concentrations of glutamate induced neuronal death. The chronic glutamate toxicity was independent of neuronal density, whereas increased density potentiated acute glutamate toxicity. Activation of ionotropic glutamate receptors (iGluRs) contributed to induction of chronic and acute glutamate toxicity at similar rates at DIV14. Inactivation of the metabotropic glutamate receptors (mGluRs) by AIDA increased neuronal sensitivity to chronic glutamate exposure but not to acute exposure. Neuronal death by acute toxicity wasmuch faster than by chronic toxicity in which activation ofmGluRs was involved. These results suggest that acute glutamate toxicity is quite different from chronic toxicity, in which activation of mGluRs is associated with resistance to glutamate toxicity.