l-Deprenyl fails to protect mesencephalic dopamine neurons and PC12 cells from the neurotoxic effect of 1-methyl-4-phenylpyridinium ion

doi:10.1016/S0006-8993(96)00898-0

Brain Research

Volume 741, Issues 1–2, 25 November 1996, Pages 68-74

https://doi.org/10.1016/S0006-8993(96)00898-0 Get rights and content

Abstract

l-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, appears to slow down the progression of Parkinson's disease. While inhibition of MAO-B activity can account for some of the effects of this substance, the basis by whichl-deprenyl slows the progression of the disease remains controversial. In recent years, a new mechanism of action has emerged that may explain the ability ofl-deprenyl to increase neuronal survival.l-deprenyl has been reported to modify gene expression and protein synthesis in astrocytes and PC12 cells. In this study, we tested the ability ofl-deprenyl to protect mouse mesencephalic cells from the toxicity of the 1-methyl-4-phenyl pyridinium ion (MPP⁺). We exposed mouse mesencephalic cell cultures to L-deprenyl (10 μM) and, 24 h later, to MPP⁺ (2.5 μM). On the fifth day afterl-deprenyl and MPP⁺ exposition, cells were washed free of drugs, and the following day they were tested for dopamine uptake, intracellular dopamine content and tyrosine hydroxylase immunoreactivity. The experiments were performed either in the presence or in the absence of glia. It was found thatl-deprenyl pretreatment failed to achieve any protection against MPP⁺ toxicity. The fall in dopamine uptake and intracellular dopamine content, and the diminution of tyrosine hydroxylase immunoreactivity observed in cells pretreated withl-deprenyl and then given MPP⁺ were not significantly different from the values observed in cells treated with MPP⁺ alone. Additional experiments performed in PC12 cells, confirmed the failure ofl-deprenyl to abolish the toxicity of MPP⁺. Our data seem to be at variance with previous reports demonstrating that the MAO-B inhibitorl-deprenyl protects dopaminergic neurons against MPP⁺ toxicity [12,20]; furthermore they do not support alternative mechanisms of action ofl-deprenyl against MPP⁺ toxicity.

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l-Deprenyl fails to protect mesencephalic dopamine neurons and PC12 cells from the neurotoxic effect of 1-methyl-4-phenylpyridinium ion

Abstract

Life Sci.

Biochem. Biophys. Res. Commun.

Life Sci.

Exp. Neurol.

Eur. J. Pharmacol.

J. Biol. Chem.

Neurosci. Lett.

Life Sci.

Neurosci. Lett.

Brain Res.

Brain Res.

Differing neurotoxic potencies of methamphetamine, mazindol, and cocaine on mesencephalic cultures

J. Neurochem.

l-Deprenyl increases GFAP immunoreactivity selectively in activated astrocytes in rat brain

NeuroReport

The potentiation of the anti-akinetic effect ofl-dopa treatment by an inhibitor of MAO-B,l-deprenyl

J. Neural Transm.

Cell damage associated with changing the medium of mesencephalic cultures in serum-free medium is mediated via N-methyl-D-aspartate receptors

J. Neurochem.