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Titolo:
DOPAMINE TRANSPORTER IS REQUIRED FOR IN-VIVO MPTP NEUROTOXICITY - EVIDENCE FROM MICE LACKING THE TRANSPORTER
Autore:
GAINETDINOV RR; FUMAGALLI F; JONES SR; CARON MG;
Indirizzi:
DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,DEPT CELL BIOL & MED,BOX 3287 DURHAM NC 27710 DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,DEPT CELL BIOL & MED DURHAM NC 27710
Titolo Testata:
Journal of neurochemistry
fascicolo: 3, volume: 69, anno: 1997,
pagine: 1322 - 1325
SICI:
0022-3042(1997)69:3<1322:DTIRFI>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
PARKINSONISM-INDUCING NEUROTOXIN; FIBRILLARY ACIDIC PROTEIN; RAT STRIATUM; MOUSE STRIATUM; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; MPP+; 1-METHYL-4-PHENYLPYRIDINIUM; METABOLITE; SEROTONIN; TOXICITY;
Keywords:
DOPAMINE TRANSPORTER; MPTP NEUROTOXICITY; MPP+; GLIAL FIBRILLARY ACIDIC PROTEIN; MICRODIALYSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
R.R. Gainetdinov et al., "DOPAMINE TRANSPORTER IS REQUIRED FOR IN-VIVO MPTP NEUROTOXICITY - EVIDENCE FROM MICE LACKING THE TRANSPORTER", Journal of neurochemistry, 69(3), 1997, pp. 1322-1325

Abstract

The neurotoxic effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) was tested on mice lacking the dopamine (DA) transporter (DAT-/-mice), Striatal tissue DA content and glial fibrillary acidic protein (GFAP) mRNA expression were assessed as markers of MPTP neurotoxicity. MPTP (30 mg/kg, s.c., b.i.d.) produced an 87% decrease in tissue DAlevels and a 29-fold increase in the level of GFAP mRNA in the striatum of wild-type animals 48 h after administration. Conversely, there were no significant changes in either parameter in DAT-/-mice. Heterozygotes demonstrated partial sensitivity to MPTP administration as shownby an intermediate Value (48%) of tissue DA loss. Direct intrastriatal infusion of tile active metabolite of MPTP, 1-methyl-4-phenylpyridinium (MPP+; 10 mM), via a microdialysis probe produced a massive effluxof DA in wild-type mice(>320-fold). in the DAT-/-mice the same treatment produced a much smaller increase in extracellular DA (sixfold), which is likely secondary to tissue damage due to the implantation of the dialysis probe. These observations show that the DAT is a mandatory component for expression of MPTP toxicity in vivo.

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Documento generato il 07/07/20 alle ore 11:51:06