Reactive oxygen species in NMDA receptor-mediated glutamate neurotoxicity

In search of endogenous protective substances that inhibit neurotoxic action of glutamate and nitric oxide (NO), we found that brain-derived neurotrophic factor (BDNF), acting on TrkB receptor tyrosine kinase, inhibited neurotoxicity induced by glutamate and NO donors in cultured cortical neurons. In co-cultures of the mesencephalon and striatum, projection of mesencephalic dopamine neurons to the striatum attenuated N-methyl-D-aspartate (NMDA)-induced cytotoxicity in dopamine neurons themselves. Growth factors such as neurotrophins, which the target cells in the striatum would synthesize and secrete, may offer the protection of dopamine neurons against glutamate neurotoxicity. (C) 1999 Elsevier Science Ltd. All rights reserved.