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Titolo:
Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in Old-World primates one year after MPTP treatment
Autore:
Elsworth, JD; Taylor, JR; Sladek, JR; Collier, TJ; Redmond, DE; Roth, RH;
Indirizzi:
Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 , Dept Psychiat, New Haven, CT 06520 USA Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA Yale Univ NewHaven CT USA 06520 Dept Pharmacol, New Haven, CT 06520 USA Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA Yale Univ NewHaven CT USA 06520 Dept Neurosurg, New Haven, CT 06520 USA Chicago Med Sch, Dept Neurosci, N Chicago, IL 60064 USA Chicago Med Sch NChicago IL USA 60064 Neurosci, N Chicago, IL 60064 USA Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USARush Presbyterian St Lukes Med Ctr Chicago IL USA 60612 ago, IL 60612 USA
Titolo Testata:
NEUROSCIENCE
fascicolo: 2, volume: 95, anno: 2000,
pagine: 399 - 408
SICI:
0306-4522(2000)95:2<399:SDCOSP>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
FETAL VENTRAL MESENCEPHALON; TREATED COMMON MARMOSET; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; SUBSTANTIA-NIGRA; BEHAVIORAL DEFICITS; LOCUS-COERULEUS; CAUDATE-PUTAMEN; BRAIN DOPAMINE; ANIMAL-MODELS; VERVET MONKEY;
Keywords:
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Parkinson's disease; caudate nucleus; putamen; nucleus accumbens; primate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Elsworth, JD Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 at, New Haven, CT 06520 USA
Citazione:
J.D. Elsworth et al., "Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in Old-World primates one year after MPTP treatment", NEUROSCIENC, 95(2), 2000, pp. 399-408

Abstract

Despite widespread use of the primate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease, there is a paucity of data concerning the relationship between striatal dopaminergic function and behavior over time. This study examines the relationship between markers of dopamine neuron integrity and dopaminergic metabolic activity in striatal subregions with the degree of parkinsonian disability in 32 monkeys treated with MPTP one year earlier. Based on the parkinsonian summary score during the month following MPTP treatment, each monkey was assigned to one of four severity categories. We called these categories "Severe", "Moderate", "Mild" and "Asymptomatic". Monkeys in the Severe category were behaviorally stable, and loss of dopamine concentration was greater than 98% in all subregions of striatum one year after MPTP treatment. This value was not significantly different from the level of depletion, reported previously, at one to two months after MPTP in Severe monkeys, and apparently this loss of striatal dopamine is beyond the level from which effective compensations can occur. The parkinsonian disabilities in monkeys of other severity groups (Moderate, Mild, Asymptomatic) improved significantly over the year, despite having mean dopamine depletion of 75-99% in different subregions of striatum at one to two months after MPTP treatment. At one year after MPTP treatment, the mean dopamine depletions in different subregions of caudate nucleus and putamen had diminished in Asymptomatics (21-81%), Milds (35-96%), and Moderates(86-97%). Dopamine loss in nucleus accumbens was relatively spared compared with most striatal subregions, yet in Severe monkeys the decrease in thisregion reached 96%. In addition, at one year after MPTP treatment, there was a significant linear relationship between parkinsonian behavioral severity category and dopamine concentration, and homovanillic acid concentrationand homovanillic acid/dopamine ratio in the striatum. The re-establishmentof dopamine levels and homovanillic acid/dopamine ratios was most pronounced in putamen, ventromedial caudate nucleus and nucleus accumbens. Thus the small difference in striatal dopamine loss that distinguishes monkeys with widely different behavior at one to two months after MPTP increases over time. We suggest that the milder the initial loss, the greater capacity there is for regeneration or sprouting of dopamine terminals, which isreflected in marked increases in dopamine levels and modest elevations of metabolic activity (homovanillic acid/dopamine ratio). With greater initiallosses, there is less capacity to increase terminal density, which is reflected later by smaller increases in striatal dopamine levels and more marked increases in metabolic activity. It appears that 5-10% of normal striataldopamine levels is sufficient for overtly normal motor performance in non-human primates. (C) 1999 IBRO. Published by Elsevier Science Ltd.

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Documento generato il 01/04/20 alle ore 11:18:42