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Titolo:
Pharmacological inactivation of the vesicular monoamine transporter can enhance 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration of midbrain dopaminergic neurons, but not locus coeruleus noradrenergic neurons
Autore:
German, DC; Liang, CL; Manaye, KF; Lane, K; Sonsalla, PK;
Indirizzi:
Univ Texas, SW Med Sch, Dept Psychiat, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 d Sch, Dept Psychiat, Dallas, TX 75390 USA Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey Piscataway NJ USA 08854 scataway, NJ 08854 USA
Titolo Testata:
NEUROSCIENCE
fascicolo: 4, volume: 101, anno: 2000,
pagine: 1063 - 1069
SICI:
0306-4522(2000)101:4<1063:PIOTVM>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROTOXIN 1-METHYL-4-PHENYLPYRIDINIUM; PARKINSONS-DISEASE; MPTP NEUROTOXICITY; KNOCKOUT MICE; MOUSE; BRAIN; MPP+; VESICLES; TOXICITY; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE;
Keywords:
immunohistochemistry; catecholamines; mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: German, DC Univ Texas, SW Med Sch, Dept Psychiat, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Psychiat, Dallas, TX 75390 USA
Citazione:
D.C. German et al., "Pharmacological inactivation of the vesicular monoamine transporter can enhance 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration of midbrain dopaminergic neurons, but not locus coeruleus noradrenergic neurons", NEUROSCIENC, 101(4), 2000, pp. 1063-1069

Abstract

The vesicular monoamine transporter in the brain can sequester the neurotoxin 1-methyl-4-phenylpyridinium into synaptic vesicles and protect catecholamine-containing neurons from degeneration. Mouse nigrostriatal dopaminergic neurons, and to a lesser extent locus coeruleus noradrenergic neurons, are vulnerable to toxicity produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The present study sought to determine whether pharmacological inactivation of the vesicular monoamine transporter in the brain would enhance the degeneration of substantia nigra dopaminergic neurons and locus coeruleus noradrenergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated animals. Mice were treated subacutely with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone, or in combination with vesicular monoamine transporter inhibitors (tetrabenazine or Ro4-1284), and 10-24 days later striatal dopamine and cortical norepinephrine levels were measured using chromatographic methods. In the same animals, substantia nigra and locus coeruleus catecholaminergic neurons were counted using tyrosine hydroxylase immunohistochemical staining with computer imaging techniques. Mice in which pharmacological blockage of the vesicular monoamine transporter enhanced the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in the depletion of striatal dopamine concentrations also exhibited enhanced degeneration of substantia nigra dopaminergic neurons. In the same animals, however, vesicular monoamine transporter blockade did not enhance the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the locus coeruleus noradrenergic system. These data are consistent with the hypothesis that the vesicular monoaminetransporter can protect catecholamine-containing neurons from 1-methyl-4-phenylpyridinium-induced degeneration by sequestration of the toxin within brain vesicular monoamine transporter-containing synaptic vesicles. Since the amount of vesicular monoamine transporter in locus coeruleus neurons is more than in substantia nigra neurons, and because 1-methyl-4-phenylpyridinium is sequestered within locus coeruleus neurons to a far greater extent than within substantia nigra neurons, it may be that a greater amount of vesicular monoamine transporter inhibition is required for 1-methyl-4-phenylpyridinium to be toxic to locus coeruleus neurons than to substantia nigra dopaminergic neurons. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 07:41:18