Comparison of glutamate and N-methyl-D-aspartate toxicities on rat mesencephalic primary cell cultures

Excitotoxicities of glutamate and NMDA were studied on primary cultures of rat embryonic substantia nigra. The toxicity of the general neuronal population (identified with neuron specific enolase-NSE) was compared with that of dopaminergic neurons (identified with TH antibodies). We have shown that there exists a time-dependent toxicity to glutamate in 9 d old cultures in vitro and exposures as short as 5 min are significantly toxic. By comparing the effects of long 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 microM) as opposed to less potent lower doses (< 500 microM). In comparison 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 glutamate toxicity by the non-competitive NMDA antagonist TCP indicates that they are more susceptible to non-NMDA mediated neurotoxicity than the general neuronal population.