Kainic acid induces selective mitochondrial oxidative phosphorylation enzyme dysfunction in cerebellar granule neurons: protective effects of melatonin and GSH ethyl ester

Kainic acid (KA), a potent central excitotoxin, may elicit neuronal death via generation of reactive oxygen species (ROS). The present study was undertaken to further characterize KA neurotoxicity and its relationship to ROS production and mitochondrial dysfunction. Exposure of rat cerebellar granule neurons at 14 days in vitro to 0.5 mM KA for 30 min resulted in the death of 53% of cells 24 h later. ROS production, evaluated by 2',7'-dichlorofluorescein diacetate, increased in KA-treated granule neurons. Resolution of mitochondrial oxidative phosphorylation enzymes by blue native polyacrylamide gel electrophoresis, followed by histochemical staining, showed that KA induced a strong decrease (\u201340%, P