Seizures evoked by mitochondrial toxin, 3-nitropropionic acid: new mechanism of epileptogenesis?

A number of data concerning the central action of mitochondrial toxins, substances impairing mitochondrial synthesis of ATP and thus compromising cellular energy status, has emerged within last years. 3-Nitropropionic acid (3-NPA) is an irreversible inhibitor of succinate dehydrogenase and mitochondrial complex II. The experimental administration of 3-NPA may lead to selective neuronal loss and chorea-like behavioral alterations but, as was recently shown, it also evokes clonic convulsions in rodents. The gathered data suggest that disturbed mitochondrial energy metabolism might initiate the chain of events culminating in seizure episode and that 3-NPA might become a useful tool in studying "mitochondrial" seizures. It has been hypothesized that the resistance to standard anticonvulsive therapy occurring among high proportion of epilepsy sufferers may result from the impairment of mitochondrial energy status due to either genetic predispositions or environmental influences.