An endogenous dopaminergic neurotoxin: implication for Parkinson's disease.
Neurodegeneration
; 4(3): 271-81, 1995 Sep.
Article
em En
| MEDLINE
| ID: mdl-8581559
ABSTRACT
Oxidation of dopamine by monoamine oxidase results in the endogenous metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). The toxicity of DOPAL for dopaminergic neurons was investigated using rat neostriatal synaptosomes, PC-12 cells and cultures of fetal rat dissociated mesencephalon. The Na(+)-dependent uptake of [3H]DOPAL in synaptosomes was inhibited by mazindol. DOPAL selectively inhibited dopamine uptake but not [14C]GABA uptake, induced membrane damage and liberation of dopamine into the medium. Incubation of PC-12 cells with 6.5 microM of DOPAL for 24 h caused degeneration of the neuritic process, and the number of viable cells were reduced by 25% of control. There were practically no surviving cells after 24 h of incubation with 33 microM of DOPAL. After 8 h of treatment with 33 microM of DOPAL, dopamine and 3,4-dihydroxyphenylacetic acid content in the cells were reduced by 38% and 53% of control. DOPAL-induced cell damage released lactic acid dehydrogenase into the incubation media. This toxic effect of DOPAL was time- and concentration-dependent. In mesencephalic cultures, after exposure to 33 microM of DOPAL, the surviving TH+ cells showed rounded cell body, and fibre network was highly reduced. These results indicate DOPAL is a neurotoxin and may be involved in the degeneration of dopaminergic neurons.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Sinaptossomos
/
Ácido 3,4-Di-Hidroxifenilacético
/
Neostriado
/
Inibidores da Captação de Dopamina
/
Terminações Nervosas
Limite:
Animals
Idioma:
En
Revista:
Neurodegeneration
Ano de publicação:
1995
Tipo de documento:
Article