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The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

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Summary

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as l-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((±)-2-carboxypiperazin-4yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease.

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Abbreviations

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate

CPP:

3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid

DOPAC:

dihydroxyphenylacetic acid

EAA:

excitatory amino acid

5-HIAA:

5-hydroxyindolacetic acid

5-HT:

serotonin

HVA:

homovanillic acid

MAO-B:

monoamine oxidase type B

MK-801:

dizocilpine

MPP+ :

1-Methyl-4-phenylpyridinium ion

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NA:

moradrenaline

NMDA:

N-methyl-d-aspartate

TH:

tyrosine hydroxylase

QUIS:

quisqualate

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Author notes

  1. Peter-Andreas Löschmann

    Present address: Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany

Authors and Affiliations

  1. Department of Clinical Neurochemistry, University of Würzburg, Füchsleinstrasse 15, D-97080, Würzburg, Germany

    Klaus W. Lange, Emin Sofic & Peter Riederer

  2. Laboratory of Psychobiology, Institute of General Psychology, University of Düsseldorf, D-40225, Düsseldorf, Germany

    Klaus W. Lange & Karl T. Kalveram

  3. Research Laboratories of Schering AG, D-13353, Berlin, Germany

    Peter-Andreas Löschmann, Matthias Burg, Reinhard Horowski & Helmut Wachtel

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  1. Klaus W. Lange
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  2. Peter-Andreas Löschmann
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  3. Emin Sofic
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Correspondence to: K. W. Lange at the above address

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Lange, K.W., Löschmann, PA., Sofic, E. et al. The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates. Naunyn-Schmiedeberg's Arch Pharmacol 348, 586–592 (1993). https://doi.org/10.1007/BF00167234

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  • DOI: https://doi.org/10.1007/BF00167234

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