Aspartate neurotoxicity on cultured cortical neurons

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Abstract
L‐aspartate neurotoxicity was quantitatively characterized in murine cortical cell cultures. Five‐minute exposure to 30 μM–3 mM L‐aspartate resulted in concentration‐dependent (ED50 about 190 μM) neuronal destruction over the next 10 hr; glia were not injured. D‐aspartate and L‐aspartate were roughly equipotent neurotoxins. Ion substitution experiments suggested that L‐aspartate neurotoxicity is comprised of both acute, sodium‐dependent “excitotoxicity” and delayed, calcium‐dependent degeneration, with the latter predominant under conditions of brief exposure. Aspartate neurotoxicity could be attenuated by D‐2‐amino‐5‐phosphonovalerate (D‐APV), dextrorphan, ketamine, and kynurenate, but not by L‐glutamate diethyl ester or gamma‐D‐glutamyl‐aminomethyl sulfonate, consistent with principal involvement of N‐methyl‐D‐aspartate receptors. DAPV and dextrorphan produced different effects on the aspartate concentration–toxicity relation; the former drug was consistent with a competitive and the latter with a noncompetitive mechanism of antagonism.