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Titolo:
MPTP-INDUCED OXIDATIVE STRESS AND NEUROTOXICITY ARE AGE-DEPENDENT - EVIDENCE FROM MEASURES OF REACTIVE OXYGEN SPECIES AND STRIATAL DOPAMINELEVELS
Autore:
ALI SF; DAVID SN; NEWPORT GD; CADET JL; SLIKKER W;
Indirizzi:
NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,HFT-132,3900 NCTRRD JEFFERSON AR 72079 UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL LITTLE ROCK AR 72205 UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL LITTLE ROCK AR 72205 ARKANSAS STATE UNIV,DEPT SCI BIOL STATE UNIV AR 72467 NIDA,ADDICT RES CTR,MOLEC NEUROPSYCHIAT SECT BALTIMORE MD 21224
Titolo Testata:
Synapse
fascicolo: 1, volume: 18, anno: 1994,
pagine: 27 - 34
SICI:
0887-4476(1994)18:1<27:MOSANA>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HYDROXYL RADICAL GENERATION; MONOAMINE OXIDASE-B; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; 1-METHYL-4-PHENYLPYRIDINIUM MPP+; INTRACRANIAL MICRODIALYSIS; CATECHOLAMINE NEURONS; SUBSTANTIA NIGRA; TOXICITY; MICE; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE;
Keywords:
AGING; DOPAMINE; MPTP; NEUROTOXICITY; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; STRIATUM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
S.F. Ali et al., "MPTP-INDUCED OXIDATIVE STRESS AND NEUROTOXICITY ARE AGE-DEPENDENT - EVIDENCE FROM MEASURES OF REACTIVE OXYGEN SPECIES AND STRIATAL DOPAMINELEVELS", Synapse, 18(1), 1994, pp. 27-34

Abstract

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes marked depletion of dopamine (DA) levels and reduction in the activity of tyrosine hydroxylase (TH) in the nigrostriatal DA pathway. In the brain, theenzyme monoamine oxidase B converts MPTP to 1-methyl-4-phenylpyridinium (MPP(+)) which enters DA terminals via DA uptake sites. Within the DA terminals, MPP(+) blocks the mitochondrial complex I and causes ATPdepletion. This is thought to be the main cause of MPTP-induced terminal degeneration. In addition, reactive oxygen species (ROS) generatedafter blockade of the complex I as well as those generated due to DA oxidation may participate in MPTP-induced dopaminotoxicity. The present study sought to determine if a single injection of a large dose of MPTP generates ROS. We also sought to determine if these changes as well as changes in DA levels were correlated and age-dependent. Toward that end, we have used C57/B6N male mice that were 22 days or 12 months old. These animals were injected with a single dose of MPTP (40 mg/kg,ip). Animals were sacrificed at various times after drug administration. MPTP produced no significant increase in ROS nor decreases in DA or HVA concentrations in the striatum of the younger mice. However, DOPAC concentrations were significantly decreased from 15-120 min after drug administration. In the older mice, MPTP caused significant increases in ROS from the beginning to the end of the study period. DA concentrations were decreased from 60 min onward. DOPAC concentrations were decreased significantly after 15-120 min while HVA concentrations weresignificantly increased after 60 and 120 min. These data demonstrate that in older mice, a single dose of MPTP can cause increases of ROS which were associated with subsequent decreases in DA concentrations. Younger mice were not similarly affected. These results suggest that MPTP-induced neurotoxicity is age-dependent and may be mediated by oxidative stress. (C) 1994 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 14:04:08