3-NITROPROPIONIC ACID INDUCES APOPTOSIS IN CULTURED STRIATAL AND CORTICAL-NEURONS

INGESTION of 3-nitropropionic acid (3-NPA) in moldy sugar cane causes brain damage in children. The mechanism of 3-NPA toxicity is thought t o be inhibition of energy production, leading to ATP depletion and exc itotoxicity. We exposed cultured mouse striatal or cortical neurons to 1-2 mM 3-NPA for 48 h. This exposure produced gradual neuronal degene ration characterized by cell body shrinkage and DNA fragmentation. Add ition of glutamate antagonists during 3-NPA exposure did not reduce ne uronal death. However, addition of the macromolecular synthesis inhibi tors cycloheximide, emetine or actinomycin D markedly reduced neuronal death. Our results do not exclude that 3-NPA can induce excitotoxicit y in more intact systems, but raise the additional possibility that 3- NPA may also act to induce neuronal apoptosis.