Protective effects of riluzole on dopamine neurons: Involvement of oxidative stress and cellular energy metabolism

Riluzole is neuroprotective in patients with amyotrophic lateral sclerosis and may also protect dopamine (DA) neurons in Parkinson's disease. We exami ned the neuroprotective potential of riluzole on DA neurons using primary r at mesencephalic cultures and human dopaminergic neuroblastoma SH-SY5Y cell s. Riluzole (up to 10 muM) alone affected neither the survival of DA neuron s in primary cultures nor the growth of SH-SY5Y cells after up to 72 h. Ril uzole (1-10 muM) dose-dependently reduced DA cell loss caused by exposure t o MPP+ in both types of cultures. These protective effects were accompanied by a dose-dependent decrease of intracellular ATP depletion caused by MPP (30-300 muM) in SH-SY5Y cells without affecting intracellular net NADH con tent, suggesting a reduction of cellular ATP consumption rather than normal ization of mitochondrial ATP production. Riluzole (1-10 muM) also attenuate d oxidative injury in both cell types induced by exposure to L-DOPA and 6-h ydroxydopamine, respectively. Consistent with its antioxidative effects, ri luzole reduced lipid peroxidation induced by Fe3+ and L-DOPA in primary mes encephalic cultures. Riluzole (10 muM) did not alter high-affinity uptake o f either DA or MPP+. However, in the same cell systems, riluzole induced ne uronal and glial cell death with concentrations higher than those needed fo r maximal protective effects (greater than or equal to 100 muM). These data demonstrate that riluzole has protective effects on DA neurons in vitro ag ainst neuronal injuries induced by (a) impairment of cellular energy metabo lism and/or (b) oxidative stress. These results provide further impetus to explore the neuroprotective potential of riluzole in Parkinson's disease.