Symptomatic and asymptomatic 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated primates: Biochemical changes in striatal regions

doi:10.1016/0306-4522(89)90212-1

Neuroscience

Volume 33, Issue 2, 1989, Pages 323-331

https://doi.org/10.1016/0306-4522(89)90212-1 Get rights and content

Abstract

Administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to primates produces an excellent behavioral model of idiopathic Parkinson's disease. In the vervet monkey, regional biochemical differences in the striatum of two 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups were examined one to two months after treatment and compared with controls; one group displayed no observable gross motor abnormalities after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment (asymptomatic), whereas the other group became markedly parkinsonian (symptomatic). In both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups massive depletions of dopamine and homovanillic acid concentrations were observed in the striatum; generally, dopamine losses in the symptomatic group (> 95%) were greater than in the asymptomatic group (> 75%). However, in striatum, a marked heterogeneity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine susceptibility was found; certain striatal regions having 99% depletion of dopamine even in asymptomatic monkeys. Overall, in ventromedial regions of striatum the losses of dopamine and homovanillic acid concentrations were less than in dorsolateral regions at the same coronal level. There was a significant negative correlation between control homovanillic acid/dopamine ratios and susceptibility of examined regions to 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine toxicity. Unlike idiopathic, but similar to postencephalitic, Parkinson's disease, dopamine and homovanillic acid levels in caudate nucleus were not spared relative to putamen; in fact, in the asymptomatic group caudate nucleus dopamine and homovanillic acid concentrations were depleted to a greater extent than in putamen.

The relatively small, but distinct, differences in dopamine and homovanillic acid depletions between asymptomatic and symptomatic monkeys in some regions indicates the potential of reversing parkinsonian motor abnormalities with intrastriatal grafts or implants that produce relatively low amounts of dopamine.

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Symptomatic and asymptomatic 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated primates: Biochemical changes in striatal regions

Abstract

J. Neurol. Sci.

Biochem. Pharmacol.

Biochem. biophys. Rex. Commun.

Life Sci.

Neurosci. Lett.

Neuroscience

Brain Res.

Life Sci.

Neurosci. Lett.

Neuroscience

Neurosci. Lett.

Brian Res.

J. biol. Chem.

Neurosci. Lett.

Neuroscience

Lancet

Brain Res.

Neuroscience

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

A. Rev. Neurosci.

Permanent human Parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases

Neurology

Herabgesetzte Konzentration der Homovanillinsaure im Gehirn von parkinsonkranken Menschen als Ausdruck der Storung des zentralen Dopaminstoffwechsels

Klin. Wschr.