흰쥐 미숙 대뇌피질 신경세포에서 quisqualate로 유발된 흥분성 세포독성에 대한 spermine의 영향

Effects of Spermine on Quisqualate-induced Excitotoxicity in Rat Immature Cortical Neurons

Glutamate (Glu) receptor-mediated excitotoxicity has been implicated in many acute and chronic types of neurological disorders. Exposure of mature rat cortical neurons (15~18 days in culture) to the various concentrations of Glu resulted in a marked neuronal death, whereas immature rat cortical neurons (4~5 days in culture) were resistant to the Glu-induced toxicity. Glu receptor subtype-specific agonists showed differential extent of toxicity in the immature neurons. The neurons treated with NMDA or kainate (KA) did not exhibit damage. However, quisqualate (QA) treatment induced a considerable cell death (36.1%) in immature neurons. The non-NMDA antagonist DNQX did not reduce this response. Interestingly, the QA-induced damage was not altered by the polyamine antagonist ifenprodil. Taken together, unlike NMDA or KA, QA can induce neurotoxicity in immature rat cortical neurons and the QA-induced toxicity was potentiated by spermine. The lack of antagonizing effects of DNQX and ifenprodil on QA-induced toxicity and the potentiated toxicity by spermine, respectively, implies that both QA receptor and the polyamine site of NMDA receptor may not mediate the neurotoxicity observed in this study, and that a distinct mechanism(s) may be involved in the excitotoxicity in immature neurons.