Transforming growth factor-beta2 increases NMDA receptor-mediated excitotoxicity in rat cerebral cortical neurons...

The ability of transforming growth factor-beta2 (TGFbeta2) to directly regulate neuronal sensitivity to glutamate and N-methyl-D-aspartate (NMDA) excitotoxicity in rat cerebral cortical neurons was investigated. Mixed neuronal-glial cultures treated with TGFbeta2 (1-10 ng/ml) exhibited a significant 25-50% increase in neuronal death compared to control cultures. TGFbeta2 potentiation of this endogenous glutamate excitotoxicity was blocked by the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate. In addition, neuronal death induced by brief NMDA exposure in both mixed neuronal-glial and pure neuronal cultures was increased by TGFbeta2 (1-30 ng/ml) with a similar dose-response curve. These findings indicate that TGFbeta2, at physiologically relevant concentrations, potentiates NMDA receptor-mediated excitotoxicity and that this occurs independently of TGFbeta2 effects on glia.