EXPOSURE TO HYDROGEN-PEROXIDE INDUCES CELL-DEATH VIA APOPTOSIS IN CULTURED RAT CORTICAL-NEURONS

To investigate whether direct oxidative damage may induce neuronal dea th via an apoptotic cell suicide pathway, we exposed cultured cortical neurons to the prooxidant hydrogen peroxide. Our experiments demonstr ate that brief exposures to low concentrations of hydrogen peroxide ca n induce neuronal cell death via apoptosis as demonstrated by toxicity assays, specific DNA staining, and the appearance of DNA laddering on agarose gels. These results suggest that direct oxidative injury may serve as a general trigger for apoptosis in the CNS, and that other ap optotic stimuli, such as exposure to amyloid-beta peptides, may also i nvolve oxidative injury. Peroxide-induced apoptosis may serve as a val uable model for further studies of apoptosis in neurons.