POLYAMINE NEUROTOXICITY IS ANTAGONIZED BY DIZOCILPINE IN CULTURED CHICK CORTICAL-NEURONS

Release of endogenous polyamines may contribute to neuronal loss in ischemia and related conditions. Primary cortical neurons were exposed to spermine and spermidine and subsequently assayed for [H-3]ouabain binding to quantify neuronal loss. Neuronal survival was significantly decreased in the presence of spermine at 24 h (500 muM), 48 h (250 muM and 500 muM) and 72 h (10-500 muM) relative to controls. Co-application of 250 muM spermine and 10 muM dizocilpine for 48 h completely inhibited the effect of spermine alone. Spermidine exposure (10-500 muM) did not alter neuronal survival at any of the time points. These data indicate that the polyamine spermine is toxic to neurons in vitro and that toxicity is prevented by the NMDA-associated channel antagonist dizocilpine.