Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey

doi:10.1016/0006-8993(84)90777-7

Brain Research

Volume 292, Issue 2, 6 February 1984, Pages 390-394

https://doi.org/10.1016/0006-8993(84)90777-7 Get rights and content

Abstract

1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) was administered via the intraperitoneal route to squirrel monkeys. Akinesia, rigidity and hypophonia were seen after repeated doses of 2 mg/kg. Postural tremor was present in one animal. Neuropathologic examination revealed cell loss restricted to the zona compacta of the substantia nigra. MPTP appears effective in producing an animal model for Parkinson's disease in the squirell monkey, and may be one of themore selective neurotoxins described to date.

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Citation Excerpt :
MPTP: MPTP is another commonly used toxin for inducing PD-like pathology in both mice and non-human primates. Animals systemically treated with MPTP are characterized with a selective destruction of dopaminergic neurons of the nigrostriatal tract and related motor deficits (Burns et al., 1983; Jenner et al., 1984; Langston et al., 1984). In non-human primates, the motor phenotype is very similar to the one seen in PD patients, i.e. akinesia, rigidity, flexed posture and difficulty swallowing (Burns et al., 1983).
Alpha-synuclein aggregates are the hallmark pathology of Parkinson's disease, which can propagate in a stereotypical pattern along the brain-body axis. Parkinson's disease patients not only display heterogeneous symptoms but also show variable patterns of alpha-synuclein pathology and affected neuronal systems during the disease course, complicating early and accurate diagnosis. Emerging data from post-mortem and imaging studies strongly suggest that disease heterogeneity could, at least in part, be explained by variable disease onset site, i.e. brain or body. This has led to the recently hypothesized formulation of two Parkinson's disease-subtypes, a body-first subtype where pathogenic alpha-synuclein arises in the body and spreads to the brain, and a brain-first subtype where pathogenic alpha-synuclein arises in the brain and spreads to the body. From a preclinical perspective, several animal models have been adapted or developed to reproduce Parkinson's disease-like pathology in the brain or periphery aiming to address the site of disease onset. Here, we review the current rodent and primate models that aim to reproduce Parkinson's disease pathology development and spreading in the brain and/or body and discuss the value and shortcomings of these models for the development of potential future applications in clinical trials and personalized medicine.

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: This study was supported in part by the Institute for Medical Research, the Medical Staff Corporation of Santa Clara Valley Medical Center and the Veterans Administration Medical Reasearch Program. We thank Mrs. Ruth Grajcer and Mrs. Roxana L. Norville for technical assistance.

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Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey

Abstract

Psychiat. Res.

A primate model of Parkinson's disease: selective destruction of substantia nigra, pars compacta dopaminergic neurons by N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a parkinsonian syndrome causing agent in man and monkey, produces different effects in guinea pig and rat

Pharmacologist