Modeling Parkinson's Disease in Primates: The MPTP Model

Abstract

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate models of Parkinson's disease (PD) reproduce most, although not all, of the clinical and pathological hallmarks of PD. The present contribution presents the possibilities offered by the MPTP monkey models of PD to readers with minimal knowledge of PD, emphasizing the diversity of species, route and regimen of administration, symptoms and pathological features. Readers would eventually find out that there is not a single MPTP monkey model of PD but instead MPTP monkey models of PD, each addressing a specific experimental need.

Animal models of neurodegenerative diseases

“…59,60 MPTP administration to nonhuman primates is the experimental model that more closely resembles the pathological features of PD, including nigrostriatal dopamine depletion and extrastriatal dopamine, noradrenaline, and serotonin changes observed in PD patients. 61 In this model, the motor symptoms are closely similar to those observed in man (akinesia, bradykinesia, rigidity, and postural abnormalities) except for rest tremor. The symptoms are also reversible by all dopaminergic drugs known to be effective in PD.…”

Effect of Ganoderma lucidum on MPTP induced behavioral alterations in Swiss albino mice

“…19,20 Since GLPS and GLTT, has combination benefit without toxicity which represents the desired end results in the development of effective therapeutics interven tions, it has been used for hundreds of years as a health promotion and treatment strategy. 21,22 In the present study, MPTP administered group showed an increased neuronal and muscular activities rather than a decrease. PD was char acterized by a decreased voluntary movement, but we observed an increased motor activity after MPTP administration and this may be due to its sympathomimetic over activation or frequency of MPTP which may not be sufficient to induce PD in experimental animals.…”

“…Porras et al induced PD in monkey and mouse and they found that "MPTP mouse models for instance failed to replicate symptomatic manifesta tion of PD". 22 GLPS and GLTT were found to alter the MTPT induced increase in behavioral function and this indicates that both GLPS and GLTT has some degree of neuroprotective effect. Zhang et al, and Zhou et al, studied the neuroprotective effect of G. lucidum and the effect is due to reduction in the percentage of apoptotic neurons, suppressed overexpression of active caspasses3, 8 and 9, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels and inhibition of the reduc tion of Bcl2 expression.…”

Une implication des fibres sérotoninergiques qui va au-delà des dyskinésies induites par la L-DOPA

“…Ce modèle consiste en la mise en place d'une lésion du système sérotoninergique chez des animaux pré-alablement rendus parkinsoniens [5]. Il est en effet possible d'induire des symptômes parkinsoniens chez le singe macaque par l'administration systé-mique de 1-méthyl-4-phényl-1,2,3,6-tétrahydropyridine (MPTP), une neurotoxine détruisant préférentiellement les neurones dopaminergiques [6]. Nous avons reproduit, dans un premier temps, les effets de l'intoxication au MPTP chez les singes [7].…”

“…‡ An implication of serotonergic fibers which goes beyond Levodopa-induced dyskinesia et qu'elles sont reliées à la lésion du système dopaminergique [8,9]. De plus, la rigidité est un symptôme qui est peu évalué dans les modèles de Parkinson développés chez les singes [6]. Lors de l'évaluation des animaux rendus parkinsoniens, nous avons observé que les animaux développaient, avant la lésion sérotoninergique, des complications après un traitement chronique par la L-DOPA.…”