A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

TLDR

N‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (NMPTP) can induce a parkinsonism‑like syndrome in primates, mirroring the pathological and biochemical alterations seen in human Parkinson’s disease. The study aimed to demonstrate that intravenous NMPTP administration in rhesus monkeys induces parkinsonism‑like symptoms that are reversible with L‑dopa. NMPTP reduces dopamine release, causes axonal swelling and dopamine accumulation in the nigrostriatal tract, leading to extensive loss of substantia nigra pars compacta neurons and marked striatal dopamine depletion. The NMPTP‑treated monkey serves as a viable model for studying parkinsonism mechanisms and testing therapeutic interventions.

Abstract

A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.