Melatonin rescues dopamine neurons from cell death in tissue culture models of oxidative stress.

Dopamine (DA) neurons are uniquely vulnerable to damage and disease. Their loss in humans is associated with diseases of the aged, most notably, Parkinson's Disease (PD). There is now a great deal of evidence to suggest that the destruction of DA neurons in PD involves the accumulation of harmful oxygen free radicals. Since the antioxidant hormone, melatonin, is one of the most potent endogenous scavengers of these toxic radicals, we tested its ability to rescue DA neurons from damage/death in several laboratory models associated with oxidative stress. In the first model, cells were grown in low density on serum-free media. Under these conditions, nearly all cells died, presumably due to the lack of essential growth factors. Treatment with 250 microM melatonin rescued nearly all dying cells (100% tau+ neurons), including tyrosine hydroxylase immunopositive DA neurons, for at least 7 days following growth factor deprivation. This effect was dose and time dependent and was mimicked by other antioxidants such as 2-iodomelatonin and vitamin E. Similarly, in the second model of oxidative stress, 250 microM melatonn produced a near total recovery from the usual 50% loss of DA neurons caused by neurotoxic injury from 2.5 microM 1-methyl-4-phenylpyridine (MPP+). These results indicate that melatonin possesses the remarkable ability to rescue DA neurons from cell death in several experimental paradigms associated with oxidative stress.