MPTP model

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a by-product of the chemical synthesis of a meperidine analog with potent heroin-like effects. MPTP can induce a parkinsonian syndrome in humans almost indistinguishable from Parkinson’s disease (PD). Its recognition as a neurotoxin occurred in early 1982, when several young drug addicts mysteriously developed a syndrome similar to PD after the intravenous use of street preparations of meperidine analogs contaminated with MPTP. Since the discovery that MPTP causes parkinsonism in humans and non-human primates as well as in various other mammalian species, it has been used extensively as a model of PD. In humans and non-human primates, MPTP produces an irreversible and severe parkinsonian syndrome that replicates almost all of the features of PD including tremor, rigidity, slowness of movement, postural instability, and even freezing. The responses, as well as the complications to traditional anti-parkinsonian therapies, are virtually identical to those seen in PD. From neuropathological data, we know that MPTP administration causes – as seen in PD, the disruption of mitochondrial oxidative phosphorylation, oxidative stress, degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and loss of striatal dopamine levels. Additionally, an increased expression of inflammatory markers is observed. On the other hand, two typical neuropathological features of PD have, until now, been lacking in the MPTP model. Firstly, according to most published reports, pigmented nuclei such as locus coeruleus have been spared, except in the SNpc, Secondly, the eosinophilic intraneuronal inclusions called Lewy bodies, characteristic of PD, have not thus far been convincingly observed in MPTP-induced Parkinsonism.