COMPARISON OF GLUTAMATE AND N-METHYL-D-ASPARTATE TOXICITIES ON RAT MESENCEPHALIC PRIMARY-CELL CULTURES

Excitotoxicities of glutamate and NMDA were studied on primary culture s of rat embryonic substantia nigra. The toxicity of the general neuro nal population (identified with neuron specific enolase-NSE) was compa red with that of dopaminergic neurons (identified with TH antibodies). We have shown that there exists a time-dependent toxicity to glutamat e in 9 d old cultures bl vitro and exposures as short as 5 min are sig nificantly toxic. By comparing the effects oi lone time exposures (24 h) to NMDA and glutamate, we can show dose-dependent toxicity; however NMDA shows a less marked effect. especially at high doses (> 500-1000 mu M) as opposed to less potent lower doses (< 500 mu M). In comparis on to the general population of NSE-positive mesencephalic neurons, TH -positive neurons seem to exhibit a similar vulnerability to EAA. The fact that TH-positive neurons are only partially protected against glu tamate toxicity by the non-competitive NMDA antagonist TCP indicates t hat they are more susceptible to non-NMDA mediated neurotoxicity than the general neuronal population. (C) 1997 ISDN. published by Elsevier Science Ltd.