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Protective Effects of Riluzole on Dopamine Neurons
Author(s) -
Storch Alexander,
Burkhardt Katrin,
Ludolph Albert C.,
Schwarz Johannes
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0752259.x
Subject(s) - riluzole , neuroprotection , pharmacology , intracellular , lipid peroxidation , oxidative stress , chemistry , mitochondrion , sh sy5y , glutamate receptor , biology , cell culture , biochemistry , neuroblastoma , receptor , genetics
Riluzole is neuroprotective in patients with amyotrophiclateral sclerosis and may also protect dopamine (DA) neurons in Parkinson'sdisease. We examined the neuroprotective potential of riluzole on DA neuronsusing primary rat mesencephalic cultures and human dopaminergic neuroblastomaSH‐SY5Y cells. Riluzole (up to 10 μ M ) alone affected neither thesurvival of DA neurons in primary cultures nor the growth of SH‐SY5Y cellsafter up to 72 h. Riluzole (1‐10 μ M ) dose‐dependently reduced DAcell loss caused by exposure to MPP + in both types of cultures.These protective effects were accompanied by a dose‐dependent decrease ofintracellular ATP depletion caused by MPP + (30‐300 μ M )in SH‐SY5Y cells without affecting intracellular net NADH content, suggestinga reduction of cellular ATP consumption rather than normalization ofmitochondrial ATP production. Riluzole (1‐10 μ M ) also attenuatedoxidative injury in both cell types induced by exposure to L‐DOPA and6‐hydroxydopamine, respectively. Consistent with its antioxidative effects,riluzole reduced lipid peroxidation induced by Fe 3+ and L‐DOPA inprimary mesencephalic cultures. Riluzole (10 μ M ) did not alterhigh‐affinity uptake of either DA or MPP + . However, in the samecell systems, riluzole induced neuronal and glial cell death withconcentrations higher than those needed for maximal protective effects(≥100 μ M ). These data demonstrate that riluzole has protectiveeffects on DA neurons in vitro against neuronal injuries induced by (a)impairment of cellular energy metabolism and/or (b) oxidative stress. Theseresults provide further impetus to explore the neuroprotective potential ofriluzole in Parkinson's disease.