Summary
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets causes a profound loss of dopamine and serotonin in the striatum. Additional daily systemic treatment of monkeys with the antioxidants ascorbic acid (100 mg/kg) and α-tocopherol (2,350 mg/kg) prior to, during and following administration of MPTP does not prevent the loss of dopamine and serotonin in the striatum, suggesting that these antioxidants are unable to protect dopaminergic neurones against neurotoxicity of MPTP.
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References
Ballard PA, Tetrud JW, Langston JW (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. Neurology 35: 949–956
Barbeau A (1984) Etiology of Parkinson's disease: a research strategy. Can J Neurol Sci 11: 24–28
Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) 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. Proc Natl Acad Sci USA 80: 4546–4550
Chiba K, Trevor A, Castagnoli N (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem Biophys Res Commun 120: 574–578
Chiba K, Trevor AJ, Castagnoli N (1985) Active uptake of MPP+, a metabolite of MPTP, by brain synptosomes. Biochem Biophys Res Commun 128: 1228–1232
Debler EA, Hashim A, Lajtha A, Sershen H (1988) Ascorbic acid and striatal transport of [3H]1-methyl-4-phenylpyridine (MPP+) and [3H]dopamine. Life Sci 42: 2553–2559
Halliwell B, Gutteridge JMC (1985) Oxygen radicals and the nervous system. Trends Neurosci 8: 22–26
Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC (1984) Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 311: 467–469
Hoppel CL, Greenblatt D, Kwok H, Arora PK, Singh MP, Sayre LM (1987) Inhibition of mitochondrial, respiration by analogs of 4-phenylpyridine and 1-methyl-4-phenylpyridinium cation (MPP+), the neurotoxic metabolite of MPTP. Biochem Biophys Res Commun 148: 684–693
Irwin I, Langston JW (1985) Selective accumulation of MPP+ in the substantia nigra: a key to neurotoxicity. Life Sci 36: 207–212
Javitch JA, Snyder SH (1985) Uptake of MPP+ by dopamine neurons explains selectivity of parkinsonism-inducing neurotoxin, MPTP. Eur J Pharmacol 106: 455–456
Jenner P, Rupinak NMJ, Rose S, Kelly E, Kilpatrick G, Lees A, Marsden CD (1984) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset. Neurosci Lett 50: 85–90
Korytowski W, Felix CC, Kalyanaraman B (1987) Evidence for the one-electron oxidation of 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+). Biochem Biophys Res Commun 147: 354–360
Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979–980
Langston JW, Forno LS, Rebert CS, Irwin I (1984) Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the squirrel monkey. Brain Res 292: 390–394
Langston JW (1988) The etiology of Parkinson's disease: new directions for research. In: Jankovic J, Tolosa E (eds) Parkinson's disease and movement disorders. Urban & Schwarzenberg, Baltimore Munich, pp 75–85
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Martinovits G, Melamed E, Cohen O, Rosemthal J, Uzzan A (1986) Systemic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurosci Lett 69: 192–197
Nicklas WJ, Vyas I, Heikkila RE (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenylpyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Life Sci 36: 2503–2508
Perry TL, Yong VW, Clavier RM, Jones K, Wright JM, Foulks JG, Wall RA (1985) Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in mouse. Neurosci Lett 60: 109–114
Przuntek H, Russ H, Henning K, Pindur U (1985) The protective effect of 1-tert.-butyl-4,4-diphenylpiperidine against the nigrostriatal neurodegeneration caused by 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine. Life Sci 37: 1195–1200
Ramsay RR, Singer TP (1986) Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, by mitochondria. J Biol Chem 261: 7585–7587
Ransom BR, Kunis DM, Irwin I, Langston JW (1987) Astrocytes convert the parkinsonism inducing neurotoxin, MPTP, to its active metabolite, MPP+. Neurosci Lett 75: 323–328
Rios C, Tapia R (1987) Changes in lipid peroxidation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium in mouse brain homogenates. Neurosci Lett 77: 321–326
Rossetti ZL, Sotgiu A, Sharp DE, Hadjiconstantinou M, Neff NH (1988) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyrdine (MPTP) and free radicals in vitro. Biochem Pharmacol 37: 4573–4574
Russ H, Mihatsch W, Kuhn W, Przuntek H (1987) MPTP model of Parkinson's disease in marmoset: radical scavengers do not prevent neurodegeneration. J Neurochem [Suppl] 48: S 159
Russ H, Mihatsch W., Gerlach M, Riederer P, Przuntek H (1990) Neurochemical and behavioural features induced by chronic low dose treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset: implications for Parkinson's disease. Neurosci Lett (submitted)
Sershen H, Reith MEA, Hashim A, Lajtha A (1985) Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity by the antioxidant ascorbic acid. Neuropharmacology 24: 1257–1259
Sinha BK, Singh Y, Krishna G (1986) Formation of superoxide and hydroxyl radicals from 1-methyl-4-phenylpyridinium ion (MPP+): reductive activation by NADPH cytochrome-P-450 reductase. Biochem Biophys Res Commun 135: 583–588
Stephan H, Baron G, Schwerdtfeger WK (1980) The brain of the common marmoset (Callithrix jacchus)—a stereotactic atlas. Springer, Berlin Heidelberg New York
Wagner J, Vitali P, Palfreyman MG, Zraika M, Hout S (1982) Simultaneous determination of 3,4-dihydroxyphenylalanine, 5-hydroxytryptophan, dopamine, 4-hydroxy-3-methoxyphenylalanine, norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5-hydroxyindoleacetic acid in rat cerebrospinal fluid and brain by high performance liquid chromatography with electrochemical detection. J Neurochem 38: 1241–1254
Wagner GC, Jarvis MF, Carelli RM (1985) Ascorbic acid reduces the dopamine depletion induced by MPTP. Neuropharmacology 24: 1261–1262
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Mihatsch, W., Russ, H., Gerlach, M. et al. Treatment with antioxidants does not prevent loss of dopamine in the striatum of MPTP-treated common marmosets: Preliminary observations. J Neural Transm Gen Sect 3, 73–78 (1991). https://doi.org/10.1007/BF02251138
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DOI: https://doi.org/10.1007/BF02251138