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Titolo:
Mouse model of Parkinsonism: A comparison between subacute MPTP and chronic MPTP/probenecid treatment
Autore:
Petroske, E; Meredith, GE; Callen, S; Totterdell, S; Lau, YS;
Indirizzi:
Univ Missouri, Sch Pharm, Div Pharmacol, Kansas City, MO 64108 USA Univ Missouri Kansas City MO USA 64108 armacol, Kansas City, MO 64108 USA Univ Missouri, Sch Pharm, Dept Basic Med Sci, Kansas City, MO 64108 USA Univ Missouri Kansas City MO USA 64108 Med Sci, Kansas City, MO 64108 USA Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England Univ Oxford Oxford England OX1 3QT pt Pharmacol, Oxford OX1 3QT, England
Titolo Testata:
NEUROSCIENCE
fascicolo: 3, volume: 106, anno: 2001,
pagine: 589 - 601
SICI:
0306-4522(2001)106:3<589:MMOPAC>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOPAMINERGIC NEUROTOXIN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; ALPHA-SYNUCLEIN; TYROSINE-HYDROXYLASE; ARBITRARY PARTICLES; BASAL GANGLIA; TOTAL NUMBER; MATURE MICE; LEWY BODIES;
Keywords:
dopamine; rotarod; stereology; striatum; substantia nigra; tyrosine hydroxylase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
71
Recensione:
Indirizzi per estratti:
Indirizzo: Lau, YS Univ Missouri, Sch Pharm, Div Pharmacol, 2411 Holmes St,M3-111, Kansas City, MO 64108 USA Univ Missouri 2411 Holmes St,M3-111 Kansas City MO USA 64108 8 USA
Citazione:
E. Petroske et al., "Mouse model of Parkinsonism: A comparison between subacute MPTP and chronic MPTP/probenecid treatment", NEUROSCIENC, 106(3), 2001, pp. 589-601

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely used to induce an animal model of Parkinsonism. The conventional mouse model, which usually involves acute or subacute injections of MPTP, results in a significant but reversible loss of dopaminergic functions. We have developed an alternative mouse model, in which co-administration of MPTP with probenecid results in the chronic loss of striatal dopamine for at least 6 months after cessation of treatment. In the present study. we compare the neurochemical, morphological and behavioral changes that occur in this alternative, chronicmodel with those in the conventional, subacute model. In the chronic model, we demonstrate an almost 80% loss of striatat dopamine and dopamine uptake 6 months after withdrawal from treatment, The neurochemical signs match unbiased stereological measures that demonstrate gradual loss of substantia nigra neurons, Rotarod performance further substantiates these findings by showing a progressive decline in motor performance. Based on the comparisons made in this study in mice, the chronic MPTP/probenecid model shows considerable improvements over the conventional. subacute MPTP model. The sustained alterations in the nigrostriatal pathway resemble the cardinal signs of human Parkinson's disease and suggest that this chronic mouse model is potentially useful to study the pathophysiology and mechanisms of Parkinsonism. It should also prove useful for the development of neuroprotection strategies. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

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Documento generato il 28/01/20 alle ore 02:31:08