Nerve growth factor potentiates the oxidative necrosis of striatal cholinergic neurons.

Abstract

We examined the effects of nerve growth factor (NGF) on free radical neurotoxicity in striatal cell cultures. Following exposure to 30 microM Fe2+ or 1 mM L-buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, striatal neurons underwent cell body swelling and then widespread death over the next 24 h. The degeneration was prevented by addition of 100 microM trolox, an antioxidant. Addition of 100 ng/ml BDNF beginning 12 h before Fe2+ or BSO potentiated necrosis of most striatal neurons after exposure to 10 microM Fe2+ or 1 mM BSO. In contrast, treatment with 100 ng/ml NGF selectively potentiated the oxidative degeneration of striatal cholinergic neurons. The present findings provide additional evidence that NGF, like other neurotrophins, can potentiate oxidative neuronal cell necrosis.