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The Use of the MPTP-Treated Mouse as an Animal Model of Parkinsonism

Published online by Cambridge University Press:  05 January 2016

Richard E. Heikkila  and
Patricia K. Sonsalla
Richard E. Heikkila*
Affiliation:
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey
Patricia K. Sonsalla
Affiliation:
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey
*
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey, U.S.A. 08854
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Abstract:

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The MPTP-treated mouse has proven to be a valuable model of parkinsonism. For example, C57 black mice treated with MPTP exhibit a large decrement in the neostriatal content of dopamine and its metabolites, a marked reduction in the capacity of neostriatal synaptosomal preparations to accumulate [3H]dopamine, a large decrease in neostriatal tyrosine hydroxylase activity, a marked loss of nerve cells in the zona compacta of the substantia nigra, and pronounced behavioral deficits. These biochemical, pathological and behavioral deficits are similarly observed in MPTP-treated primates and in humans with idiopathic parkinsonism. A great deal of our current knowledge concerning MPTP has come from experimentation carried out in the mouse.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 14 , Issue S3 , August 1987 , pp. 436 - 440
Copyright
Copyright © Canadian Neurological Sciences Federation 1987

References

REFERENCES

1.Davis, GC, Williams, AC, Markey, SP, et al. Chronic parkinsonism secondary lo intravenous injection of meperidine analogues. Psych Res 1979; 1: 249–254.CrossRefGoogle Scholar
2.Langston, JW, Ballard, P, Tetrud, JW, Irwin, I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219: 979–980.CrossRefGoogle ScholarPubMed
3.Burns, RS, LeWitt, PA, Ebert, MH, et al. The clinical syndrome of striatal dopamine deficiency; parkinsonism induced by 1-methyl-4-phenyl-1.2,3,6-tetrahydropyridine (MPTP).? Engl J Med 1985; 312: 1418–1421.CrossRefGoogle ScholarPubMed
4.Burns, RS, Chiueh, CC, Markey, SP, et al. 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 1983: 80: 4546–4550.CrossRefGoogle ScholarPubMed
5.Ward, CD, Duvoisin, RC, Ince, SE.et al. Parkinson’s disease in 65 pairs of twins and in a set of quadruplets. Neurology 1983: 33: 815–824.CrossRefGoogle Scholar
6.Duvoisin, RC.Is Parkinson’s disease acquired or inherited? Can J Neurol Sci 1984; 11: 151–155.CrossRefGoogle ScholarPubMed
7.Forno, LS.Langston, JW, DeLanney, LE.et al. Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 1986; 20: 449–455.CrossRefGoogle ScholarPubMed
8.Chiueh, CC, Markey, SP, Burns, RS, et al. Neurochemical and behavioral effects of systemic and intranigral administration of N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine in the rat. Eur J Pharmacol 1984; 100: 189–194.CrossRefGoogle Scholar
9.Heikkila, RE, Hess, A, Duvoisin, RC.Dopaminergic neurotoxicity of l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine in mice. Science 1984; 224: 1451–1453.CrossRefGoogle Scholar
10.Heikkila, RE, Manzino, L, Cabbat, FS, Duvoisin, RC.Protection against the dopaminergic neurotoxicity of l-methyl-4-phenyl-l, 2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984; 311: 467–469.CrossRefGoogle Scholar
11.Markey, SP, Johannessen, JN.Chiueh, CC, et al. Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 1984; 311: 464–467.CrossRefGoogle ScholarPubMed
12.Sonsalla, PK, Heikkila, RE.The influence of dose and dosing interval on MPTP-induced dopaminergic neurotoxicity in mice. Eur J Pharmacol 1986: 129: 339–345.CrossRefGoogle ScholarPubMed
13.Heikkila, RE.Differential neurotoxicity of l-methyl-4-phenyl-l ,2, 3,6-tetrahydropyridine (MPTP) in Swiss-Webster mice from different sources. Eur J Pharmacol 1985; 117: 131–133.CrossRefGoogle Scholar
14.Fuller, RW, Hemrick-Luecke, SK.Influence of selective, reversible inhibitors of monoamine oxidase on the prolonged depletion of striatal dopamine by l-methyl-4-phenyl-l,2.3.6-tetrahydropyridine in mice. Life Sci 1985; 37: 1089–1096.CrossRefGoogle Scholar
15.Gupta, MD, Felten, DL, Gash, DM.MPTP alters central catecholamine neurons in addition to the nigrostriatal system. Br Res Bull 1984; 13: 737–742.CrossRefGoogle Scholar
16.Perry, TL, Yong, VW, Clavier, RM.et al. Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse. Neurosci Lett 1985; 60: 109–114.CrossRefGoogle ScholarPubMed
17.Schmidt, CJ, Bruckwick, E, Lovenberg, W.Lack of evidence supporting a role for dopamine in l-methyl-4-phenyl-l ,2,3,6-tetrahydropyridine neurotoxicity. Eur J Pharmacol 1985; 113: 149–150.CrossRefGoogle Scholar
18.Sundstrom, E, Jonsson, G.Pharmacological interference with the neurotoxic action of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse. Eur J Pharmacol 1985; 110: 293–299.CrossRefGoogle Scholar
19.Wallace, RA, Boldry, R, Schmittgen, T, et al. Effect of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) on monoamine neurotransmitters in mouse brain and heart. Life Sci 1984; 35: 285–291.CrossRefGoogle Scholar
20.Melamed, E, Rosenthal, J, Globus, M, et al. Mesolimbic dopaminergic neurons are not spared by MPTP neurotoxicity in mice. Eur J Pharmacol 1985: 114: 97–100.CrossRefGoogle Scholar
21.Mayer, RA, Walters, AS, Heikkila, RE.l-Methyl-4-phenyl-l,2,3, 6-tetrahydropyridine (MPTP) administration to C57-black mice leads to parallel decrements in neostriatal dopamine content and tyrosine hydroxylase activity. Eur J Pharmacol 1986; 120: 375–377.CrossRefGoogle Scholar
22.Langston, JW, Irwin, I, Langston, EB, Forno, LS.Pargyline prevents MPTP-induced parkinsonism in primates. Science 1984; 225: 1480–1482.CrossRefGoogle ScholarPubMed
23.Cohen, G, Pasik, P, Cohen, B, et al. Pargyline and deprenyl prevent the neurotoxicity of l-methyl-4-phenyl-l ,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur J Pharmacol 1984; 106: 209–210.CrossRefGoogle Scholar
24.Javitch, JA.D’Amato, RJ, Strittmatter, SM, Snyder, SH.Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci, USA 1985: 82: 2173–2177.CrossRefGoogle Scholar
25.Pileblad, E, Carlsson, A.Catecholamine-uptake inhibitors prevent the neurotoxicity of I-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse brain. Neuropharmacol 1985; 24: 689–692.CrossRefGoogle Scholar
26.Mayer, RA, Kindt, MV, Heikkila, RE.Prevention of the nigrostriatal toxicity of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by inhibitors of 3,4-dihydroxyphenylethylamine transport. J Neurochem 1986; 47: 1073–1079.CrossRefGoogle Scholar
27.Ricaurte, GA, Langston, JW, DeLanney, LE, et al. Dopamine uptake blockers protect against the dopamine depleting effect of l-methyl-4-phenyl-l ,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum. Neurosci Lett 1985; 59: 259–264.CrossRefGoogle Scholar
28.Castagnoli, N Jr, Chiba, K, Trevor, AJ.Potential bioactivation path-ways for the neurotoxin l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Life Sci 1985; 36: 225–230.CrossRefGoogle Scholar
29.Fuller, RW, Robertson, DW, Hemrick-Luecke, SK.Persistent depletion of striatal dopamine in mice by l-methyl-4-(2-thienyl)-l ,2,3, 6-tetrahydropyridine (MPTP). Biochem Pharmacol 1986; 35: 143–144.CrossRefGoogle Scholar
30.Youngster, SK, Duvoisin, RC, Hess, A, et al. l-Methyl-4-(2’methylphenyl)-l,2,3,6-tetrahydropyridine (2’-CH3-MPTP) is a more potent dopaminergic neurotoxin than MPTP in mice. Eur J Pharmacol 1986; 122: 283–287.CrossRefGoogle Scholar
31.Youngster, SK, Sonsalla, PK, Heikkila, RE.Evaluation of the biological activity of several analogs of the dopaminergic neurotoxin l-methyl-4-phenyl-1,23,6-tetrahydropyridine. J Neurochem 1987; 48: 929–934.CrossRefGoogle Scholar
32.Bradbury, AJ, Costall, B, Domeney, AM, et al. The toxic actions of MPTP and its metabolite MPP+ are not mimicked by analogues of MPTP lacking an N-methyl moiety. Neurosci Lett 1985; 61: 121–126.CrossRefGoogle Scholar
33.Heikkila, RE, Youngster, SK, Sonsalla, PK, et al. The role of monoamine oxidase-B (MAO-B) in the dopaminergic neurotoxicity induced by l-methyl-4-(2’ methylphenyl)-l,2,3,6-tetrahydro-pyridine (2’ CH3-MPTP). Soc Neurosci Abstr 1986; 12: 1394.Google Scholar