The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: A PET, histological and biochemical study

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dc.contributor.authorBlesa, J.
dc.contributor.authorPifl, C.
dc.contributor.authorSanchez-Gonzalez, M. A.
dc.contributor.authorJuri, C.
dc.contributor.authorGarcia-Cabezas, M. A.
dc.contributor.authorAdanez, R.
dc.contributor.authorIglesias, E.
dc.contributor.authorCollantes, M.
dc.contributor.authorPenuelas, I.
dc.contributor.authorSanchez-Hernandez, J. J.
dc.contributor.authorRodriguez-Oroz, M. C.
dc.contributor.authorAvendano, C.
dc.contributor.authorHornykiewicz, O.
dc.contributor.authorCavada, C.
dc.contributor.authorObeso, J. A.
dc.date.accessioned2025-01-20T23:56:59Z
dc.date.available2025-01-20T23:56:59Z
dc.date.issued2012
dc.description.abstractParkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET (F-18-DOPA K-i and C-11-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features. (C) 2012 Elsevier Inc. All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.nbd.2012.05.018
dc.identifier.eissn1095-953X
dc.identifier.issn0969-9961
dc.identifier.urihttps://doi.org/10.1016/j.nbd.2012.05.018
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95183
dc.identifier.wosidWOS:000307694400009
dc.issue.numero1
dc.language.isoen
dc.pagina.final91
dc.pagina.inicio79
dc.revistaNeurobiology of disease
dc.rightsacceso restringido
dc.subjectMPTP monkey
dc.subjectParkinson's disease
dc.subjectPET
dc.subjectAAAD
dc.subjectCompensatory mechanisms
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: A PET, histological and biochemical study
dc.typeartículo
dc.volumen48
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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