LEVODOPA INDUCES APOPTOSIS IN CULTURED NEURONAL CELLS - A POSSIBLE ACCELERATOR OF NIGROSTRIATAL DEGENERATION IN PARKINSONS-DISEASE

Apoptosis is an active, intrinsic cell suicide program. We recently su ggested that it may have a role in the death of nigrostriatal dopamine rgic neurons in Parkinson's disease (PD). We now report that levodopa, the current major therapy for PD, is a potent inducer of apoptosis in cultured postmitotic chick sympathetic neurons. Levodopa, in a concen tration range of 0.01-0.3 mM, caused the characteristic apoptotic casc ade of cell shrinkage, massive membrane blebbing, and nuclear fragment ation, as evident by nuclear flow cytometry and fluorescence microscop y. Levodopa-induced apoptosis was inhibited by antioxidants, indicatin g that it may be mediated by autooxidation-reactive species. Levodopa treatment for PD may therefore constitute an additional challenge for the defective apoptosis-inhibiting systems in the nigrostriatal neuron s. Despite reassuring data from some, but not all, previous studies, t hese findings suggest that the possible in vivo toxic effects of levod opa on the survival of the remaining nigral neurons should be further explored.