CALRETININ-IMMUNOREACTIVE DOPAMINERGIC-NEURONS FROM EMBRYONIC RAT MESENCEPHALON ARE RESISTANT TO LEVODOPA-INDUCED NEUROTOXICITY

Levodopa, which is used in the treatment of Parkinson's disease, has k nown cytotoxic effects on dopaminergic neurons grown in culture. Calre tinin (CR) is a cytosolic calcium-binding protein found in specific su bpopulations of neurons as well as in some nonneuronal tissue. CR is e xpressed in 10% of rat embryo dopaminergic neurons grown in vitro. Sin ce it has been postulated that CR provides neuroprotection due to its calcium-binding properties, we investigated whether CR-containing dopa minergic neurons were spared from levodopa toxicity. Incubation of mes encephalic cells with 10(-5) to 10(-7) M levodopa on Days 1-6 in vitro produced no significant effects on the number of dopaminergic neurons containing CR, but resulted in the loss of approximately 65% of the d opaminergic cells which did not contain CR. The remaining CR-negative dopaminergic neurons exhibited dose-dependent reductions in neurite le ngth. The neuronal processes in CR-containing dopaminergic cells retai ned a smooth bipolar appearance. CR-immunoreactive cells which did not contain dopamine showed slight neurite length decreases at the highes t drug concentrations but no changes in neuron number. These results i ndicate that CR may protect dopaminergic neurons from levodopa-induced toxicity. (C) 1997 Academic Press.