NITRIC-OXIDE AND SUPEROXIDE CONTRIBUTE TO MOTOR-NEURON APOPTOSIS INDUCED BY TROPHIC FACTOR DEPRIVATION

Primary cultures of rat embryonic motor neurons deprived of brain-deri ved neurotrophic factor (BDNF) induce neuronal nitric oxide synthase ( NOS) within 18 hr. Subsequently, >60% of the neurons undergo apoptosis between 18 and 24 hr after plating. Nitro-L-arginine and nitro-L-argi nine methyl ester (L-NAME) prevented motor neuron death induced by tro phic factor deprivation. Exogenous generation of nitric oxide at conce ntrations lower than 100 nM overcame the protection by L-NAME. Mangane se tetrakis (4-benzoyl acid) porphyrin, a cell-permeant superoxide sca venger, also prevented nitric oxide-dependent motor neuron death. Moto r neurons cultured without trophic support rapidly became immunoreacti ve for nitrotyrosine when compared with motor neurons incubated with B DNF, L-NAME, or manganese TBAP. Our results suggest that peroxynitrite , a strong oxidant formed by the reaction of NO and superoxide, plays an important role in the induction of apoptosis in motor neurons depri ved of trophic factors and that BDNF supports motor neuron survival in part by preventing neuronal NOS expression.