MPP+ produces progressive neuronal degeneration which is mediated by oxidative stress.

Abstract:

:The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which produces Parkinsonism, is mediated by its metabolite 1-methyl-4-phenylpyridinium ion (MPP+). When injected into the striatum MPP+ is accumulated by dopaminergic nerve terminals and is then retrogradely transported to the substantia nigra compacta. The mechanism by which it mediates cell death involves both inhibition of complex I of the electron transport chain and free radical generation. In the present experiments we found that administration of the free radical spin trap N-tert-butyl-alpha-(2-sulfophenyl) nitrone (S-PBN) significantly attenuated substantia nigra cell loss produced by MPP+ administration into rat striatum. We also found that coadministration of coenzyme Q10 with nicotinamide, which attenuates energy depletion, significantly blocked MPP(+)-induced substantia nigra damage. Last, we found that a single administration of MPP+ into rat striatum can produce progressive cell loss in the substantia nigra and that administration of S-PBN starting 7 days after administration of MPP+ can block the ensuing neuronal damage. These observations suggest that a one-time exposure to a neurotoxic agent may result in progressive neuronal degeneration mediated by oxidative stress.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Fallon J,Matthews RT,Hyman BT,Beal MF

doi

10.1006/exnr.1997.6416

subject

Has Abstract

pub_date

1997-03-01 00:00:00

pages

193-8

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(97)96416-5

journal_volume

144

pub_type

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