Abstract
1-Methyl–4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most selective neurotoxins. However, this is not the sole reason it has gained widespread recognition. Rather, the spectacular way that its biologic effects were first recognized, which was a direct result of the clandestine manufacture of illicit drugs (1), thrust this previously obscure compound squarely into the limelight. Although in retrospect at least one earlier case had been reported (2), a direct association between exposure to MPTP and central nervous system damage was not made until the early 1980s, when a group of young heroin abusers in northern California mysteriously developed parkinsonism after using a new “designer drug” known as China White. The cause of their clinical syndrome was eventually traced back to a contaminant of the “synthetic heroin,” which proved to be MPTP (3).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Lewin, R. (1984) Trail of ironies to Parkinson’s disease. Science 224, 1083–1085.
Davis, G. C., Williams, A. C., Markey, S. E, Ebert, M. H., Caine, E. D., Reichert, C. M., and Kopin, I. J. (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res. 1, 249–254.
Langston, J. W., Ballard, P. A., Tetrud, J. W., and Irwin, I. (1983) Chronic parkinsonism in humans due to a product of meperidine analog synthesis. Science 219, 979–980.
Langston, J. W. and Ballard, P. A. (1984) Parkinsonism induced by 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP): Implications for treatment and the pathogenesis of Parkinson’s disease. Can. J. Neurol. Sci. 11, 160–165.
Ballard, P. A., Tetrud, J. W., and Langston, J. W. (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Seven cases. Neurology 35, 949–956.
Ruttenber, A. J., Garbe, P. L., Kalter, H. D., Castro, K. G., Tetrud, J. W., Porter, P., Irwin, I., and Langston, J. W. (1986) Meperidine analog exposure in California narcotics abusers: Initial epidemiologic findings, in MPTP: A Neurotoxin Producing a Parkinsonian Syndrome ( Markey, S. P., Castagnoli, N., Jr., Trevor, A. J., and Kopin, I. J., eds.), Academic, New York, pp. 339–353.
Tetrud, J. W. and Langston, J. W. (1992) Tremor in MPTP-induced parkinsonism. Neurology 42, 407–410.
Tetrud, J. W., Langston, J. W., Garbe, P. L., and Ruttenber, A. J. (1989) Mild parkinsonism in persons exposed to 1-methy1–4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neurology 39, 1483–1487.
Caine, D. B., Langston, J. W., Martin, W. R. W., Stoessl, A. J., Ruth, T. J., Adam, M. J., Pate, B. D., and Schulzer, M. (1985) Positron emission tomography after MPTP: observations relating to the cause of Parkinson’s disease. Nature 317, 246–248.
Martin, W. R. W., Palmer, M. R., Patlak, C. S., and Caine, D. B. (1989) Nigrostriatal function in humans studied with positron emission tomography. Ann. Neurol. 26, 535–542.
Widner, H., Tetrud, J. W., Rehncrona, S., Brundin, P., Bjorklund, A., Lindvall, O., and Langston, J. W. (1993) Fifteen months follow-up on bilateral embryonic mesencephalic grafts in two cases of severe MPTP-induced parkinsonism, in Advances in Neurology, vol. 60, Parkinson’s Disease: From Basic Research to Treatment. Proceedings of the 10th International Symposium on Parkinson’s Disease ( Narabayashi, H., Nagatsu, T., Yanagisawa, N., and Mizuno, Y., eds.), Raven, New York, pp. 729–733.
Stern, Y. and Langston, J. W. (1985) Intellectual changes in patients with MPTP-induced parkinsonism. Neurology 35, 1506–1509.
Stern, Y., Tetrud, J. W., Martin, W. R. W., Kutner, S. J., and Langston, J. W. (1990) Cognitive change following MPTP exposure. Neurology 40, 261–264.
Weihmuller, F B., Hadjiconstantinou, M., and Bruno, J. P. (1988) Acute stress or neuroleptics elicit sensorimotor deficits in MPTP-treated mice. Neurosci. Lett. 85, 137–142.
Ricaurte, G. A., Langston, J. W., DeLanney, L. E., Irwin, I., Peroutka, S. J., and Forno, L. S. (1986) Fate of nigrostriatal neurons in young mature mice given 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine: A neurochemical and morphological reassessment. Brain Res. 376, 117–124.
Boyce, S., Kelly, E., Reavill, C., Jenner, P., and Marsden, C. D. (1984) Repeated administration of N-methyl-4-pheny1–1,2,5,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurons. Biochem. Pharmacol. 33, 1747–1752.
Chiueh, C. C., Markey, S. P., Burns, R. S., Johannessen, J. N., Pert, A., and Kopin, I. J. (1984) Neurochemical and behavioral effects of systemic and intranigral administration of N-methyl-4-pheynl-1,2,3,6-tetrahydropyridine in the rat. Eur. J. Pharmacol. 100, 189–194.
Sahgal, A., Andrews, J. S., Biggins, J. A., Candy, J. M., Edwardson, J. A., Keith, A. B., Turner, J. D., and Wright, C. (1984) N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) affects locomotor activity without producing a nigrostriatal lesion in the rat. Neurosci. Lett. 48, 179–184.
Donnan, G. A., Kaczmarczyk, S. J., Solopotias, T., Rowe, P. J., Kalnins, R. M., Vajda, F. J. E., and Mendelsohn, F. A. O. (1986) The neurochemical and clinical effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in small animals. Clin. Exp. Neurol. 22, 155–164.
Jarvis, M. F. and Wagner, G. C. (1990) 1-Methy1–4-phenyl-1,2,3,6-tetrahydropyridineinduced neurotoxicity in the rat: Characterization and age-dependent effects. Synapse 5, 104–112.
Heikkila, R. E., Manzino, L., Cabbat, F. S., and Duvoisin, R. C. (1984) Protection against the dopaminergic neurotoxicity of 1-methyl-4-pheynl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 311, 467–469.
Sonsalla, P. K. and Heikkila, R. E. (1988) Neurotoxic effects of 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine in several strains of mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 12, 345–354.
Gupta, M., Gupta, B. K., Thomas, R., Bruemmer, V., Sladek, J. R., Jr., and Felten, D. L. (1986) Aged mice are more sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine than young adults. Neurosci. Lett. 70, 326–331.
Mori, S., Fujitake, J., Kuno, S., and Sano, Y. (1988) Immunohistochemical evaluation of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons of young adult mice using dopamine and tyrosine hydroxylase antibodies. Neurosci. Lett. 90, 57–62.
Seniuk, N. A., Tatton, W. G., and Greenwood, C. E. (1990) Dose-dependent destruction of the coeruleus-cortical and nigral-striatal projections by MPTP. Brain Res. 527, 7–20.
Ricaurte, G. A., Irwin, I., Forno, L. S., DeLanney, L. E., Langston, E. B., and Langston, J. W. (1987) Aging and MPTP-induced degeneration of dopaminergic neurons in the substantia nigra. Brain Res. 403, 43–51.
Chan, P., Di Monte, D. A., Langston, J. W., and Janson, A. M. (1997) (+)MK-801 does not prevent MPTP-induced loss of nigral neurons in mice. J. Pharmacol. Exp. Ther. 280, 439–446.
Irwin, I., DeLanney, L. E., Forno, L. S., Finnegan, K. T., Di Monte, D. A., and Langston, J. W. (1990) The evolution of nigrostriatal neurochemical changes in the MPTP-treated squirrel monkey. Brain Res. 531, 242–252.
Burns, R. S., Chiueh, C. C., Markey, S. P., Ebert, M. H., Jacobowitz, D. M., and Kopin, I. J. (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6tetrahydropyridine. Proc. Natl. Acad. Sci. USA 80, 4546–4550.
Langston, J. W., Forno, L. S., Rebert, C. S., and Irwin, I. (1984) Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in the squirrel monkey. Brain Res. 292, 390–394.
Langston, J. W., Irwin, I., Langston, E. B., and Forno, L. S. (1984) Pargyline prevents MPTP-induced parkinsonism in primates. Science 225, 1480–1482.
Cohen, G., Pasik, P., Cohen, B., Leist, A., Mytilineou, C., and Yahr, M. D. (1985) Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur. J. Pharmacol. 106, 209–210.
Jenner, P., Rose, S. P., Nomoto, M., and Marsden, C. D. (1986) MPTP-induced parkinsonism in the common marmoset: behavioral and biochemical effects. Adv. Neurol. 45, 183–186.
Di Monte, D. A. and Langston, J. W. (1993) MPTP-induced parkinsonism in nonhuman primates, in Current Concepts in Parkinson’s Disease Research ( Schneider, J. S. and Gupta, M., eds.), Hogrefe and Huber Publishers, Toronto, pp. 159–179.
Tetrud, J. W., Langston, J. W., Redmond, D. E., Jr., Roth, R. H., Sladek, J. R., Jr., and Angel, R. W. (1986) MPTP-induced tremor in human and non-human primates [Abstract]. Neurology 36 (Suppl. 1), 308.
Clarke, C. E., Boyce, S., Robertson, R. G., Sambrook, M. A., and Crossman, A. R. (1989) Drug-induced dyskinesia in primates rendered hemiparkinsonian by intracarotid administration of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP). J. Neurol. Sci. 90, 307–314.
Schneider, J. S. (1989) Levodopa-induced dyskinesias in Parkinsonian monkeys: Relationship to extent of nigrostriatal damage. Pharmacol. Biochem. Behavior 34, 193–196.
Schneider, J. S., Unguez, G. A., Yuwiler, A., Berg, S. C., and Markham, C. H. (1988) Deficits in operant behaviour in monkeys treated with N-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP). Brain 111, 1265–1285.
Schneider, J. S. (1990) Chronic exposure to low doses of MPTP. II. Neurochemical and pathological consequences in cognitively-impaired, motor asymptomatic monkeys. Brain Res. 534, 25–36.
Schneider, J. S. and Kovelowski, C. J., II (1990) Chronic exposure to low doses of MPTP. I. Cognitive deficits in motor asymptomatic monkeys. Brain Res. 519, 122–128.
Kish, S. J., Shannak, K., and Hornykiewicz, 0. (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. N. Engl. J. Med. 318 (14), 876–880.
Elsworth, J. D., Deutch, A. Y., Redmond, D. E., Jr., Sladek, J. R., Jr., and Roght, R. H. (1987) Differential responsiveness to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in subregions of the primate substantia nigra and striatum. Life Sci. 40, 193–202.
Pifl, C., Schingnitz, G., and Hornykiewicz, 0. (1988) The neurotoxin MPTP does not reproduce in the rhesus monkey the interregional pattern of striatal dopamine loss typical of human idiopathic Parkinson’s disease. Neurosci. Lett. 92, 228–233.
Moratalla, R., Quinn, B., DeLanney, L. E., Irwin, I., Langston, J. W., and Graybiel, A. M. (1992) Differential vulnerability of primate caudate-putamen and striosome-matrix dopamine systems to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. USA 89, 3859–3863.
Wüllner, U., Pakzaban, P., Brownell, A.-L., Hantraye, P., Burns, L., Shoup, T., Elmaleh, D., et al. (1994) dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys. A positron emission tomography study with 11C-CFT. Exp. Neurol. 126, 305–309.
Goldman, J. E., Yen, S. H., Chiu, F. C., and Peress, N. S. (1983) Lewy bodies of Parkinson’s disease contain neurofilament antigens. Science 221, 1082–1084.
Forno, L. S., Sternberger, L. A., Sternberger, N. H., Strefling, A. M., Swanson, K., and Eng, L. F. (1986) Reaction of Lewy bodies with antibodies to phosphorylated and nonphosphorylated neurofilaments. Neurosci. Lett. 64, 253–258.
Galloway, P. G., Grundke-Iqbal, I., Iqbal, K., and Perry, G. (1988) Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 47, 654–663.
Love, S., Saitoh, T., Saitoh, T., Quijada, S., Cole, G. M., and Terry, R. D. (1988) Alz-50, ubiquitin, and tau reactivity of neurofibrillary tangles, Pick bodies and Lewy bodies. J. Neuropathol. Exp. Neurol. 47, 393–405.
Bancher, C., Lassmann, H., Budka, H., Jellinger, K. A., Grundke-Iqbal, I., Iqbal, K., Wiche, G., Seitelberger, F., and Wisniewski, H. M. (1989) An antigenic profile of Lewy bodies: Immunocytochemical indication for protein phosphorylation and ubiquitination. J. Neuropathol. Exp. Neurol. 48, 81–93.
Forno, L. S., Langston, J. W., DeLanney, L. E., Irwin, I., and Ricaurte, G. A. (1986) Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann. Neurol. 20, 449–455.
Forno, L. S., Langston, J. W., DeLanney, L. E., and Irwin, I. (1988) An electron microscopic study of MPTP-induced inclusion bodies in an old monkey. Brain Res. 448, 150–157.
Langston, J. W., Irwin, I., Langston, E. B., and Forno, L. S. (1984) 1-Methyl-4-phenylpyridinium ion (MPP+): Identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci. Lett. 48, 87–92.
Markey, S. P., Johannessen, J. N., Chiueh, C. C., Burns, R. S., and Herkenham, M. A. (1984) Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 311, 464–467.
Irwin, I. and Langston, J. W. (1985) Selective accumulation of MPP+ in the substantia nigra: A key to neurotoxicity? Life Sci. 36, 207–212.
Riachi, N. J., Harik, S. I., Kalaria, R. N., and Sayre, L. M. (1988) On the mechanisms underlying 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. II. Susceptability among mammalian species correlates with the toxin’s metabolic patterns in brain microvessels and liver. J. Pharmacol. Exp. Ther. 244 (2), 443–448.
Sayre, L. M., Arora, P. K., Iacofano, L. A., and Harik, S. I. (1986) Comparative toxicity of MPTP, MPP+ and 3,3-dimethyl-MPDP+ to dopaminergic neurons of the rat substantia nigra. Eur. J. Pharmacol. 124, 171–174.
Castagnoli, N., Jr., Chiba, K., and Trevor, A. J. (1985) Potential bioactivation pathways for the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Life Sci. 36 (3), 225–230.
Chiba, K., Peterson, L. A., Castagnoli, K. P., Trevor, A. J., and Castagnoli, N., Jr. (1985) Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Drug Metab. Dispos. 13, 342–347.
Singer, T. P., Salach, J. I., Castagnoli, N., Jr., and Trevor, A. J. (1986) Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases. Biochem. J. 235, 785–789.
Chiba, K., Trevor, A. J., and Castagnoli, N., Jr. (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem. Biophys. Res. Commun. 120, 574–578.
Mytilineou, C. and Cohen, G. (1984) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon. Science 225, 529–531.
Sanchez-Ramos, J. R., Barrett, J. N., Goldstein, M., Weiner, W. J., and Hefti, F. (1986) 1-Methyl-4-phenylpyridinium (MPP+) but not 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in cultures of dissociated rat mesencephalic neurons. Neurosci. Lett. 72 215–220.
Di Monte, D. A., Wu, E. Y., Irwin, I., DeLanney, L. E., and Langston, J. W. (1992) Production and disposition of 1-methyl-4-phenylpyridinium in primary cultures of mouse astrocytes. Glia 5, 48–55.
Bradbury, A. J., Costall, B., Domeney, A. M., Jenner, P., Kelly, M. E., Marsden, C. D., and Naylor, R. J. (1986) 1-Methyl-4-phenylpyridine is neurotoxic to the nigrostriatal dopamine pathway. Nature 319, 56–57.
Irwin, I., Ricaurte, G. A., DeLanney, L. E., and Langston, J. W. (1988) The sensitivity of nigrostriatal dopamine neurons to MPP+ does not increase with age. Neurosci. Lett. 87, 51–56.
Fuller, R. W. and Hemrick-Luecke, S. K. (1985) Influence of selective, reversible inhibitors of monoamine oxidase on the prolonged depletion of striatal dopamine by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Life Sci. 37, 1089–1096.
Kalaria, R. N., Mitchell, M. J., and Hank, S. I. (1987) Correlation of 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity. Proc. Natl. Acad. Sci. USA 84, 3521–3525.
Reinhard, J. F., Jr., Diliberto, E. J., Jr., Viveros, O. H., and Daniels, A. J. (1987) Sub-cellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells. Proc. Natl. Acad. Sci. USA 84, 8160–8164.
Reinhard, J. F., Jr., Carmichael, S. W., and Daniels, A. J. (1990) Mechanisms of toxicity and cellular resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4phenylpyridinium in adrenomedullary chromaffin cell cultures. J. Neurochem. 55, 311–320.
Reinhard, J. F., Jr., Daniels, A. J., and Viveros, O. H. (1988) Potentiation by reserpine and tetrabenazine of brain catecholamine depletions by MPTP (i-methyl-4-phenyl1,2,3,6-tetrahydropyridine) in the mouse: Evidence for subcellular sequestration as basis for cellular resistance to the toxicant. Neurosci. Lett. 90, 349–353.
Levitt, P., Pintar, J. E., and Breakefield, X. O. (1982) Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc. Natl. Acad. Sci. USA 79, 6385–6389.
Westlund, K. N., Denney, R. M., Kochersperger, L. M., Rose, R. M., and Abell, C. W. (1985) Distinct monoamine oxidase A and B populations in primate brain. Science 230, 181–183.
Chiba, K., Trevor, A. J., and Castagnoli, N., Jr. (1985) Active uptake of MPP+, a metabolite of MPTP, by brain synaptosomes. Biochem. Biophys. Res. Commun. 128, 1229–1232.
Javitch, J. A., D’Amato, R. J., Strittmatter, S. M., and Snyder, S. H. (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: Uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc. Natl. Acad. Sci. USA 82, 2173–2177.
Ransom, B. R., Kunis, D. M., Irwin, I., and Langston, J. W. (1987) Astrocytes convert the parkinsonism-inducing neurotoxin, MPTP, to its active metabolite, MPP+. Neurosci. Lett. 75, 323–328.
Schinelli, S., Zuddas, A., Kopin, I. J., Barker, J. L., and Di Porzio, U. (1988) 1-Methyl4-phenyl-1,2,3,6-tetrahydropyridine metabolism and 1-methyl-4-phenylpyridinium uptake in dissociated cell cultures from the embryonic mesencephalon. J. Neurochem. 50, 1900–1907.
Di Monte, D. A., Wu, E. Y., Irwin, I., DeLanney, L. E., and Langston, J. W. (1991) Biotransformation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in primary cultures of mouse astrocytes. J. Pharmacol. Exp. Ther. 258, 594–600.
Scotcher, K. P., Irwin, I., DeLanney, L. E., Langston, J. W., and Di Monte, D. A. (1991) Mechanism of accumulation of the 1-methyl-4-phenylpyridinium species into mouse brain synaptosomes. J. Neurochem. 56, 1602–1607.
Reinhard, J. F., Daniels, A. J., and Painter, G. R. (1990) Carrier-independent entry of 1-methyl-4-phenylpyridinium (MPP+) into adrenal chromaffin cells as a consequence of charge delocalization. Biochem. Biophys. Res. Commun. 168, 1143–1148.
Irwin, I., Langston, J. W., and DeLanney, L. E. (1987) 4-Phenylpyridine (4PP) and MPTP: The relationship between striatal MPP+ concentrations and neurotoxicity. Life Sci. 40, 731–740.
Riachi, N. J., Arora, P. K., Sayre, L. M., and Harik, S. I. (1988) Potent neurotoxic fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs as potential probes in models of Parkinson’s disease. J. Neurochem. 50, 1319–1321.
Cashman, J. R. and Ziegler, D. M. (1986) Contribution of N-oxygenation to the metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by various liver preparations. Mol. Pharmacol. 29, 163–167.
Arora, P. K., Riachi, N. J., Harik, S. I., and Sayre, L. M. (1988) Chemical oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its in vivo metabolism in rat brain and liver. Biochem. Biophys. Res. Commun. 152, 1339–1347.
Di Monte, D. A., Wu. E. Y., and Langston, J. W. (1992) Role of astrocytes in MPTP metabolism and toxicity. Ann. NY Acad. Sci. 648, 219–228.
Melamed, E., Rosenthal, J., Globus, M., Cohen, O., and Uzzan, A. (1985) Suppression of MPTP-induced dopaminergic neurotoxicity in mice by nomifensine and L-dopa. Brain Res. 342, 401–404.
Ricaurte, G. A., Langston, J. W., DeLanney, L. E., Irwin, I., and Brooks, J. D. (1985) Dopamine uptake blockers protect against the dopamine depleting effects of 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum. Neurosci. Lett. 59, 259–264.
Sundstrom, E., Goldstein, M., and Jonsson, G. (1986) Uptake inhibition protects nigrostriatal dopamine neurons from the neurotoxicity of 1-methyl-4-phenylpyridine (MPP+) in mice. Eur. J. Pharmacol. 131, 289–292.
Mayer, R. A., Kindt, M. V., and Heikkila, R. E. (1986) Prevention of MPTP-induced neurotoxicity by dopamine uptake inhibitors, in MPTP; A Neurotoxin Producing a Parkinsonian Syndrome ( Markey, S. P., Castagnoli, N., Jr., Trevor, A. J., and Kopin, I. J., eds.), Academic, Orlando, FL, pp. 585–590.
Schultz, W., Scarnati, E., Sundstrom, E., Tsutsumi, T., and Jonsson, G. (1986) The catecholamine uptake blocker nomifensine protects against MPTP-induced parkinsonism in monkeys. Exp. Brain Res. 63, 216–220.
Schultz, W., Scarnati, E., Sundstrom, E., and Romo, R. (1989) Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism by the catecholamine uptake inhibitor nomifensine: Behavioral analysis in monkeys with partial striatal dopamine depletions. Neuroscience 31, 219–230.
Takada, M., Li, Z. K., and Hattori, T. (1990) Astroglial ablation prevents MPTP-induced nigrostriatal neuronal death. Brain Res. 509, 55–61.
Javitch, J. A., Uhl, G. R., and Snyder, S. H. (1984) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: characterization and localization of receptor binding sites in rat and human brain. Proc. Natl. Acad. Sci. USA 81, 4591–4595.
Santiago, M., Machado, A., and Cano, J. (1996) Nigral and striatal comparative study of the neurotoxic action of 1-methyl-4-phenylpyridinium ion: involvement of dopamine uptake system. J. Neurochem. 66, 1182–1190.
Mitchell, I. J., Cross, A. J., Sambrook, M. A., and Crossman, A. R. (1986) N-methyl-4phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the monkey: neurochemical pathology and regional brain metabolism. J. Neural Transm. XX, 41–46.
Schneider, J. S., Yuwiler, A., and Markham, C. H. (1987) Selective loss of subpopulations of ventral mesencephalic dopaminergic neurons in the monkey following exposure to MPTP. Brain Res. 411, 144–150.
German, D. C., Durach, A., Askari, S., Speciale, S. G., and Bowden, D. M. (1988) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonien syndrome in macaca fascicularis: Which midbrain dopaminergic neurons are lost? Neuroscience 24, 161–174.
Parent, A., Lavoie, B., Smith, Y., and Bedard, P. J. (1990) The dopaminergic nigropallidal projection in primates: Distinct cellular origin and relative sparing in MPTPtreated monkeys. Adv. Neurol. 53, 111–116.
D’Azur, V. (1786) Traite d’anatomie et de physiologie, cited by Marsden, C. D.: brain melanin in Pigments in Pathology, 1969, (Wolman, M., ed.), Academic, New York, pp. 395–420.
Graham, D. G. (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol. Pharmacol. 14, 633–643.
Marsden, C. D. (1983) Neuromelanin and Parkinson’s disease. J. Neural Transm. Suppl. 19 121–141.
Forno, L. S. (1966) Pathology of parkinsonism-a preliminary report of 24 cases. J. Neurosurg. 24, 266–271.
Forno, L. S. and Alvord, E. C., Jr. (1974) Depigmentation in the nerve cells of the substantia nigra and locus coeruleus in parkinsonism. Adv. Neurol. 5, 195–202.
Mann, D. M. A. and Yates, P. O. (1983) Possible role of neuromelanin in the pathogenesis of Parkinson’s disease. Mech. Age Dev. 21, 193–203.
Lindquist, N. G., Larsson, B. S., and Lyden-Sokolowski, A. (1987) Neuromelanin and its possible protective and destructive properties. Pigment Cell Res. 1, 133–136.
Commoner, B., Townsend, J., and Pake, G. E. (1954) Free radicals in biological materials. Nature 174, 689–691.
McGinness, J. and Proctor, P. (1973) The importance of the fact that melanin is black. J. Theor. Biol. 39, 677–680.
Gan, E. V., Haberman, H. F., and Menon, I. A. (1976) Electron transfer properties of melanin. Arch. Biochem. Biophys. 173, 666–672.
Lindquist, N. G. (1972) Accumulation in vitro of 35S-chlorpromazine in the neuromelanin of human substantia nigra and locus coeruleus. Arch. Int. Pharmacodyn. Ther. 200, 190–195.
Salazar, M., Sokoloski, T. D., and Patil, P. N. (1978) Binding of dopaminergic drugs by the neuromelanin of the substantia nigra, synthetic melanins and melanin granules. Fed. Proc. 37, 2403–2407.
Swartz, H. M., Sarna, T., and Zecca, L. (1992) Modulation by neuromelanin of the availability and reactivity of metal ions. Ann. Neurol. 32 Suppl., S69 - S75.
Youdim, M. B. H., Ben-Shachar, D., and Riederer, P. (1994) The enigma of neuromelanin in Parkinson’s disease substantia nigra. J. Neural Transm. Suppl. 43 113–122.
Marsden, C. D. (1969) Brain melanin, in Pigments in Pathology ( Wolman, M., ed.), Academic, New York, pp. 395–420.
Barden, H. and Levine, S. (1983) Histochemical observations on rodent brain neuromelanin. Brain Res. Bull. 10, 847–851.
Herrero, M. T., Hirsch, E. C., Kastner, A., Ruberg, M., Luquin, M. R., Laguna, J., Javoy-Agid, F., Obeso, J. A., and Agid, Y. (1993) Does neuromelanin contribute to the vulnerability of catecholaminergic neurons in monkeys intoxicated with MPTP. Neuroscience 56, 499–511.
D’Amato, R. J., Lipman, Z. P., and Snyder, S. H. (1986) Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin Science 231, 987–989.
D’Amato, R. J., Benham, D. F., and Snyder, S. H. (1987) Characterization of the binding of N-methyl-4-phenylpyridine, the toxic metabolite of the parkinsonian neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to neuromelanin. J. Neurochem. 48, 653–658.
Lindquist, N. G., Lyden-Sokolowski, A., and Larsson, B. S. (1986) Accumulation of a parkinsonism-inducing neurotoxin in melanin-bearing neurons: Autoradiographic studies on 3H-MPTP. Acta Phamacol. Toxicol. 59, 161–164.
D’Amato, R. J., Alexander, G. M., Schwartzman, R. J., Kitt, C. A., Price, D. L., and Snyder, S. H. (1987) Evidence for neuromelanin involvement in MPTP-induced neurotoxicity. Nature 327, 324–326.
Wu, E. Y., Chiba, K., Trevor, A. J., and Castagnoli, N., Jr. (1986) Interactions of the 1-methyl-4-phenyl-2,3-dihydropyridinium species with synthetic dopamine-melanin. Life Sci. 39, 1695–1700.
Korytowski, W., Felix, C. C., and Kalyanaraman, B. (1987) Mechanism of oxidation of 1-methyl-4-phenyl-2,3,-dihydropyridinium (MPDP+). Biochem. Biophys. Res. Commun. 144 (2), 692–698.
Melamed, E., Soifer, D., Rosenthal, J., Pikarsky, E., and Reches, A. (1987) Effect of intrastriatal and intranigral administration of synthetic neuromelanin on the dopaminergic neurotoxicity of MPTP in rodents. Neurosci. Lett. 83, 41–46.
Pileblad, E., Nissbrandt, H., and Carlsson, A. (1984) Biochemical and functional evidence for a marked dopamine releasing action of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) in mouse brain. J. Neural Transm. 60, 199–203.
Chang, G. D. and Ramirez, V. D. (1986) The mechanism of action of MPTP and MPP+ on endogenous dopamine release from the rat corpus striatum superfused in vitro. Brain Res. 368, 134–140.
Sirinathsinghji, D. J. S., Heavens, R. P., and McBride, C. S. (1988) Dopamine-releasing action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4phenylpyridine (MPP+) in the neostriatum of the rat as demonstrated in vivo by the push-pull perfusion technique: Dependence on sodium but not calcium ions. Brain Res. 443, 101–116.
Huang, S.-J. and Chiueh, C. C. (1990) Calcium-dependent potentiation of potassium depolarization-evoked release of dopamine from nigrostriatal (A9) terminals by picomoles of MPP+. FASEB J. 4, A605 — A608.
Lang, K., Huang, S.-J., Miyake, H., and Chiueh, C. C. (1990) Calcium ion fluxes mediate sustained release of endogenous striatal dopamine by toxic doses of MPP+ in vivo. FASEB J. 4, A605.
Kupsch, A., Gerlack, M., Pupeter, S. C., et al. (1995) Pretreatment with nimodipine prevents MPTP-induced neurotoxicity at the nigral but not at the striatal level in mice. Neuroreport 6, 621–625.
Schmidt, C. J., Matsuda, L. A., and Gibb, J. W. (1984) In vitro release of tritiated monoamines from rat CNS tissue by the neurotoxic compound 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine. Eur. J. Pharmacol. 103, 255–260.
Wilson, J. A., Lau, Y. S., Gleeson, J. G., and Wilson, J. S. (1991) The action of MPTP on synaptic transmission is affected by changes in Ca2+ concentrations. Brain Res. 541, 342–346.
Chiueh, C. C. and Huang, S.-J. (1991) MPP+ enhances potassium evoked striatal release through a S2,-conotoxin-insensitive, tetrodotoxin-and nimodipine-sensitive calcium dependent mechanism. Ann. NY Acad. Sci. 635, 393–396.
Wilson, J. A., Wilson, J. S., and Weight, F. F. (1986) MPTP causes a non-reversible depression of synaptic transmission in mouse neostriatal brain slice. Brain Res. 368, 357–360.
Mayer, R. A., Kindt, M. V., and Heikkila, R. E. (1986) Prevention of the nigrostriatal toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by inhibitors of 3,4-dihydroxyphenylethylamine transport. J. Neurochem. 47, 1073–1079.
Johnson, E. A., Wu, E. Y., Rollema, H., Booth, R. G., Trevor, A. J. and Castagnoli, N., Jr. (1989) 1-Methyl-4-phenylpyridinium (MPP+) analogs: In vivo neurotoxicity and inhibition of striatal synaptosomal dopamine uptake. Eur. J. Pharmacol. 166 65–74.
Athwal, N. S. S., Ramsden, D. B., Simpson, M., and Williams, A. C. (1996) Inhibition of dopamine uptake into PC-12 cells by analogues of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP). Parkinsonism and Related Disorders 2 (1), 1–6.
Berman, S. B., Zigmond, M. J., and Hastings, T. G. (1996) Dopamine transport function: modulation by oxidative stress, in Neurodegenerative Diseases 1995: Molecular and Cellular Mechanisms and Therapeutic Advances—XVth Washington International Symposium, Washington, DC ( Fiskum, G., ed.), Plenum, New York, p. 136.
Ramassamy, C., Girbe, R, Christen, Y., and Cosentin, J. (1995) Peroxidation of synaptosomes alters the dopamine uptake complex but spares the exocytotic release of dopamine. Neurodegeneration 4 (2), 155–160.
Drukarch, B., Schepens, H. T. W. J., Langeveld, C. H., and Stoof, J. C. (1996) The vesicular storage properties of the nigro-striatal dopaminergic projection are involved in its high sensitivity to reactive oxygen species, in Neurodegenerative Diseases 1995: Molecular and Cellular Mechanisms and Therapeutic Advances, XVth Washington International Symposium, Washington, DC ( Fiskum, G., ed.), Plenum, New York, p. 67.
Stern-Bach, Y., Keen, J. N., Bejerano, M., Steiner-Mordoch, S., Wallach, M., Findlay, J. B. C., and Schuldiner, S. (1992) Homology of a vesicular amine transporter to a gene conferring resistance to 1-methyl-4-phenylpyridinium. Proc. Natl. Acad. Sci. USA 89, 9730–9733.
Vaccari, A., Del Zompo, M., Melis, F., Gessa, G. L., and Rossetti, Z. L. (1991) Interaction of 1-methyl-4-phenylpyridinium ion and tyramine with a site putatively involved in the striatal vesicular release of dopamine. Br. J. Pharmacol. 104, 573–574.
Schuldiner, S., Steiner-Mordoch, S., Yelin, R., Wall, S. C., and Rudnick, G. (1993) Amphetamine derivatives interact with both plasma membrane and secretory vesicle biogenic amine transporters. Mol. Pharmacol. 44, 1227–1231.
Lesch, K. P., Heils, A., and Riederer, P. (1996) The role of neurotransporters in excitotoxicity, neuronal cell death, and other neurodegenerative processes. J. Mol. Med. 74, 365–378.
Liu, Y., Roghani, A., and Edwards, R. H. (1992) Gene transfer of a reserpine-sensitive mechanism of resistance to N-methyl-4-phenylpyridinium. Proc. Natl. Acad. Sci. USA 89, 9074–9078.
Sundstrom, E. and Jonsson, G. (1985) Pharmacologoical interferance with the toxic action of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse. Eur. J. Pharmacol. 110, 293–299.
Pifl, C., Hornykiewicz, O., Giros, B., and Caron, M. G. (1996) Catecholamine transporters and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity: studies comparing the cloned human noradrenaline and human dopamine transporter. J. Pharmacol. Exp. Ther. 277 (3), 1437–1443.
Mavridis, M., Degryse, A.-D., Lategan, A. J., Marien, M. R., and Colpaert, E. C. (1991) Effects of locus coeruleus lesions on Parkinsonian signs, striatal dopamine and substantia nigra cell loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys: A possible role for the locus coeruleus in the progression of Parkinson’s disease. Neuroscience 41, 507–523.
Marien, M., Briley, M., and Colpaert, F. (1993) Noradrenaline depletion exacerbates MPTP-induced striatal dopamine loss in mice. Eur. J. Pharmacol. 236, 487–489.
Bing, G., Zhang, Y., Watanabe, Y., McEwen, B. S., and Stone, E. A. (1994) Locus coeruleus lesions potentiate neurotoxic effects of MPTP in dopaminergic neurons of the substantia nigra. Brain Res. 668, 261–265.
Fornai, F., Alessandri, M. G., Fascetti, E, Vaglini, E, and Corsini, G. U. (1995) Clonidine suppresses 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced reductions of striatal dopamine and tyrosine hydroxylase activity in mice. J. Neurochem. 65, 704–709.
Chiueh, C. C. (1988) Dopamine in the extrapyramidal motor function: A study based upon the MPTP-induced primate model of parkinsonism. Ann. NY Acad. Sci. 515, 226–238.
Miyake, H. and Chiueh, C. C. (1989) Effects of MPP+ on the release of serotonin and 5-hydroxyindoleacetic acid from rat striatum in vivo. Eur. J. Pharmacol. 166, 49–55.
Pérez-Otaho, I., Herrero, M. T., Oset, C., de Ceballos, M. L., Luquin, M. R., Obeso, J. A., and Del R’o, J. (1991) Extensive loss of brain dopamine and serotonin induced by chronic administration of MPTP in the marmoset. Brain Res. 567, 127–132.
Mitra, N., Mohanakumar, K. P., and Ganguly, D. K. (1992) Dissociation of serotoninergic and dopaminergic components in acute effects of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine in mice. Brain Res. Bull. 28, 355–364.
Soubrie, P., Reisine, T. D., and Glowinski, J. (1984) Functional aspects of serotonin transmission in the basal ganglia: a review and in vivo approach using the push-pull cannula technique. J. Neurosci. 13, 605–625.
Benloucif, S. and Galloway, M. P. (1991) Facilitation of dopamine release in vivo by serotonin agonists: pharmacological characterization. Eur. J. Pharmacol. 200, 1–8.
Bonhomme, N., de Deuwaerdere, P., Le Moal, M., and Spampinato, U. (1995) Evidence for 5-HT4 receptor subtype involvement in the enhancement of striatal dopamine release induced by serotonin: a microdialysis study in the halothane-anesthetized rats. Neuropharmacology 34, 269–279.
Andrews, D. W., Patrick, R. L., and Burchas, J. (1978) The effects of 5-hydroxytryptophan and 5-hydroxytryptamine on dopamine synthesis and release in rat brain striatal synaptosomes. J. Neurochem. 30, 465–470.
de Deuwaerdere, R, Bonhomme, N., Lucas, G., Le Moal, M., and Spampinato, U. (1996) Serotonin enhances striatal dopamine outflow in vivo through dopamine uptake sites. J. Neurochem. 66, 210–215.
Melamed, E., Pikarski, E., Goldberg, A., Rosenthal, J., Uzzan, A., and Conforti, N. (1986) Effect of serotonergic, corticostriatal and kainic acid lesions on the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Brain Res. 399, 178–180.
Melamed, E., Rosenthal, J., Cohen, O., Globus, M., and Uzzan, A. (1985) Dopamine but not norepinephrine or serotonin uptake inhibitors protect mice against neurotoxicity of MPTP. Eur. J. Pharmacol. 116, 179–181.
Gaspar, P., Febvret, A., and Colombo, J. (1993) Serotonergic sprouting in primate MTP-induced hemiparkinsonism. Exp. Brain Res. 96, 100–106.
Bus, J. S. and Gibson, J. E. (1984) Paraquat: model for oxidant-initiated toxicity. Environ. Health Perspect. 55, 37–46.
Frank, D. M., Arora, P. K., Blumer, J. L., and Sayre, L. M. (1987) Model study on the bioreduction of paraquat, MPP+, and analogs. Evidence against a “redox cycling” mechanism in MPTP neurotoxicity. Biochem. Biophys. Res. Commun. 147, 1095–1104.
Linkous, C. A., Schaich, K. M., Forman, A., and Borg, D. C. (1988) An electrochemical study of the neurotoxin 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine and its oxidation products. Bioelectrochem. Bioenerget. 19, 477–490.
Di Monte, D. A., Sandy, M. S., Ekstrom, G., and Smith, M. T. (1986) Comparative studies on the mechanisms of paraquat and 1-methyl-4-phenylpyridine (MPP+) cytotoxicity. Biochem. Biophys. Res. Commun. 137, 303–309.
Ekstrom, G., Di Monte, D. A., Sandy, M. S., and Smith, M. T. (1987) Comparative toxicity and antioxidant activity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its moanamine oxidase B-generated metabolites in isolated hepatocytes and liver microsomes. Arch. Biochem. Biophys. 255, 14–18.
Santiago, M., Rollema, H., De Vries, J. B., and Westerink, B. H. C. (1991) Acute effects of intranigral application of MPP+ on nigral and bilateral striatal release of dopamine simultaneously recorded by microdialysis. Brain Res. 538, 226–230.
Matsubara, K., Idzu, T., Kobayashi, Y., Gonda, T., Okunishi, H., and Kimura, K. (1996) Differences in dopamine efflux induced by MPP+ and b-carbolinium in the striatum of conscious rats. Eur. J. Pharmacol. 315, 145–151.
Spina, M. B. and Cohen, G. (1989) Dopamine turnover and glutathione oxidation: Implications for Parkinson disease. Proc. Natl. Acad. Sci. USA 86, 1398–1400.
Werner, R. and Cohen, G. (1991) Intramitochondrial formation of oxidized glutathione during the oxidation of benzylamine by monoamine oxidase. FEBS Lett. 280 (1), 44–46.
Chiueh, C. C., Miyake, H., and Peng, M.-T. (1993) Role of dopamine, autoxidation, hydroxyl radical generation, and calcium overload in underlying mechanisms involved in MPTP-induced parkinsonism, in Advances in Neurology, vol. 60, Parkinson’s Disease: From Basic Research to Treatment. Proceedings of the 10th International Symposium on Parkinson’s Disease ( Narabayashi, H., Nagatsu, T., Yanagisawa, N., and Mizuno, Y., eds.), Raven, New York, pp. 251–258.
Irwin, I. and Langston, J. W. (1995) Endogenous toxins as potential etiologic agents in Parkinson’s disease, in Etiology of Parkinson’s Disease (Ellenberg, J. H., Koller, W. C., and Langston, J. W., eds.), Marcel Dekker, New York, pp. 153–201.
Barbeau, A., Poirier, J., Dallaire, L., Rucinska, E., Buu, N. T., and Donaldson, J. (1986) Studies on MPTP, MPP+ and paraquat in frogs and in vitro, in MPTP: A Neurotoxin Producing A Parkinsonian Syndrome ( Markey, S. P., Castagnoli, N., Jr., Trevor, A. J., and Kopin, I. J., eds.), Academic, Orlando, FL, pp. 85–103.
Tse, D. C. S., McCreery, R., and Adams, R. N. (1976) Potential oxidative pathways of brain catecholamines. J. Med. Chem. 19 (1), 37–40.
Graham, D. G., Tiffany, S. M., Bell, W. R., Jr., and Gutknecht, W. E (1978) Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro. Mol. Pharmacol. 14, 644–653.
Hastings, T. G., Lewis, D. A., and Zigmond, M. J. (1996) Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections. Proc. Natl. Acad. Sci. USA 93, 1956–1961.
Hornykiewicz, 0. (1974) The mechanisms of action of L-dopa in Parkinson’s disease. Life Sci. 15, 1249–1259.
Hefti, F., Melamed, E., Bhawan, J., and Wurtman, R. J. (1981) Long-term administration of L-dopa does not damage dopaminergic neurons in the mouse. Neurology 31, 1194–1195.
Perry, T. L., Yong, V. W., Ito, M., Foulks, J. G., Wall, R. A., Godin, D. V., and Clavier, R. M. (1984) Nigrostriatal dopaminergic neurons remain undamaged in rats given high doses of L-dopa and carbidopa chronically. J. Neurochem. 43, 990–993.
Tetrud, J. W. and Langston, J. W. (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science 245, 519–522.
Parkinson Study Group (1989) Effect of deprenyl on the progression of disabililty in early Parkinson’s disease. N. Engl. J. Med. 321, 1364–1371.
Myllyla, V. V., Sotaniemi, K. A., Vuorinen, J. A., and Heinonen, E. H. (1992) Selegiline as initial treatment in de novo parkinsonian patients. Neurology 42, 339–343.
Lichter, D., Kurlan, R., Miller, C., and Shoulson, I. (1988) Does pergolide slow the progression of Parkinson’s disease? A 7-year follow-up study [Abstract]. Neurology 38, 122.
Zimmerman, T. and Sage, J. I. (1989) Long-term pergolide treatment and progression of Parkinson’s disease [Abstract]. Neurology 39, 200.
Zimmerman, T. and Sage, J. I. (1991) Comparison of combination pergolide and levodopa to levodopa alone after 63 months of treatment. Clin. Neuropharm. 14, 165–169.
Knoll, J. (1988) Extension of life span of rats by long-term (-) deprenyl treatment. Mt. Sinai J. Med. 55 (1), 67–74.
Felten, D. L., Felten, S. Y., Fuller, R. W., Romano, T. D., Smalstig, E. B., Wong, D. T., and Clemens, J. A. (1992) Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged-Fischer-344 rats. Neurobiol. Aging 13, 339–351.
Felten, D. L., Felten, S. Y., Steece-Collier, K., Date, I., and Clemens, J. A. (1992) Age-related decline in the dopaminergic nigrostriatal system: The oxidative hypothesis and protective strategies. Ann. Neurol. 32 Suppl., S133 - S136.
Sofic, E., Riederer, P., Heinsen, H., Beckmann, H., Reynolds, G. P., Hebenstreit, G., and Youdim, M. B. H. (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J. Neural Transm. 74, 199–205.
Sofic, E., Paulus, W., Jellinger, K. A., Riederer, P., and Youdim, M. B. H. (1991) Selective increase of iron in substantia nigra zona compacta of Parkinsonian brains. J. Neurochem. 56, 978–982.
Halliwell, B. and Gutteridge, J. M. C. (1985) The importance of free radicals and catalytic metal ions in human diseases. Mol. Aspects Med. 8, 89–193.
Mochizuki, H., Imai, H., Endo, K., Yokomizo, K., Murata, Y., Hattori, N., and Mizuno, Y. (1994) Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. Neurosci. Lett. 168, 251–253.
Mash, D. C., Pablo, J., Buck, B. E., Sanchez-Ramos, J. R., and Weiner, W. J. (1991) Distribution and number of transferrin receptors in Parkinson’s disease and in MPTPtreated mice. Exp. Neurol. 114, 73–81.
Poirier, J., Donaldson, J., and Barbeau, A. (1985) The specific vulnerability of the substantia nigra to MPTP is related to the presence of transition metals. Biochem. Biophys. Res. Commun. 128, 25–33.
Di Monte, D. A., Schipper, H. M., Hetts, S., and Langston, J. W. (1995) Iron-mediated bioactivation of MPTP in glial cultures. Glia 15, 203–206.
Jenner, P., Dexter, D. T., Schapira, A. H. V., and Marsden, C. D. (1990) Free radical involvement and altered iron metabolism as a cause of Parkison’s disease, in The Assessment of Therapy of Parkinsonism ( Marsden, C. D. and Fahn, S., eds.), Parthenon, New Jersey, pp. 17–30.
Earle, K. M. (1968) Studies on Parkinson’s disease including X-ray fluorescent spectroscopy of formalin fixed brain tissue. J. Neuropathol. Exp. Neurol. 27 (1), 1–14.
Dexter, D. T., Carter, C. J., Wells, R R., Agid, E J., Agid, Y., Lees, A. J., Jenner, P., and Marsden, C. D. (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J. Neurochem. 52, 381–389.
Hirsch, E. C., Brandel, J.-P., Galle, P., Agid, F. J., and Agid, Y. (1991) Iron and aluminum increase in the substantia nigra of patients with Parkinson’s disease: An x-ray microanalysis. J. Neurochem. 56, 446–451.
Schipper, H. M. (1991) Gomori-positive astrocytes: biological properties and implications for neurologic and neuroendocrine disorders. Glia 4, 365–377.
Dexter, D. T., Wells, F. R., Agid, F. J., Agid, Y., Lees, A. J., Jenner, P., and Marsden, C. D. (1987) Increased nigral iron content in postmortem parkinsonian brain. Lancet 2, 1219–1220.
Riederer, P., Sofic, E., Rausch, W. D., Schmidt, B., Reynolds, G. P., Jellinger, K. A., and Youdim, M. B. H. (1989) Transition metals, ferritin, glutathione, and ascorbic acid in Parkinsonian brains. J. Neurochem. 52, 515–520.
Ryvlin, P., Broussolle, E., Piollet, H., Viallet, F., Khalfallah, Y., and Chazon, G. (1995) Magnetic resonance imaging evidence of decreased putamenal iron content in idiopathic Parkinson’s disease. Arch. Neurol. 52 (6), 583–588.
Aisen, P. (1992) Entry of iron into cells: a new role for the transferrin receptor in modulating iron release from transferrin. Ann. Neurol. 32, s62 - s68.
Faucheux, B. A., Herrero, M. T., Villares, J., Levy, R., Javoy-Agid, E, Obeso, J. A., Hauw, J. J., Agid, Y., and Hirsch, E. C. (1995) Autoradiographic localization and density of [125I]ferrotransferrin binding sites in the basal ganglia of control subjects, patients with Parkinson’s disease and MPTP-lesioned monkeys. Brain Res. 691, 115–124.
Connor, J. R., Snyder, B. S., Arosio, P., Loeffler, D. A., and LeWitt, P. A. (1995) A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer’s diseased brains. J. Neurochem. 65, 717–724.
Leveugle, B., Faucheux, B. A., Bouras, C., Nillesse, N., Spik, G., Hirsch, E. C., Agid, Y., and Hof, P. R. (1996) Cellular distribution of the iron-binding protein lactotransferring in the mesencephalon of Parkinson’s disease cases. Acta Neuropathol. 91, 566–572.
Loeffler, D. A., Connor, J. R., Juneau, P. L., Snyder, B. S., Kanaley, L., DeMaggio, A. J., Nguyen, H., Brickman, C. M., and LeWitt, P. A. (1995) Transferrin and iron in normal, Alzheimer’s disease, and Parkinson’s disease brain regions. J. Neurochem. 65, 710–716.
Hill, J. M. (1989) Comments on “Putative biological mechanisms of the effect of iron deficiency on brain chemistry and behavior.” Am. J. Clin. Nutr. 50, 616–617.
Di Monte, D. A., Chan, P., and Sandy, M. S. (1992) Glutathione in Parkinson’s disease: A link between oxidative stress and mitochondrial damage. Ann. Neurol. 32 Suppl., S 111 — S115.
Starke, P. E. and Farber, J. L. (1985) Ferric iron and superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. Evidence for the participation of hydroxyl radicals formed by an iron-catalyzed Haber-Weiss reaction. J. Biol. Chem. 260, 10,099–10, 104.
Rossetti, Z. L., Sotgiu, A., Sharp, D. E., Hadjiconstantinou, M., and Neff, N. H. (1988) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and free radicals in vitro. Biochem. Pharmacol. 37(23) 4573–4574.
Wu, R.-M., Chiueh, C. C., Pert, A., and Murphy, D. L. (1993) Apparent antioxidant effect of 1-deprenyl on hydroxyl radical formation and nigral injury elicited by MPP+ in vivo. Eur. J. Pharmacol. 243, 241–247.
Hasegawa, E., Takeshige, K., Oishi, T., Murai, Y., and Minakami, S. (1990) 1-Methyl4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles. Biochem. Biophys. Res. Commun. 170, 1049–1055.
Cleeter, M. W. J., Cooper, J. M., and Schapira, A. H. V. (1992) Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridinium: Evidence for free radical involvement. J. Neurochem. 58, 786–789.
Poirier, J. and Barbeau, A. (1985) A catalyst function for MPTP in superoxide formation. Biochem. Biophys. Res. Commun. 131 (3), 1284–1289.
Przedborski, S., Kostic, V., Jackson-Lewis, V., Naini, A. B., Simonetti, S., Fahn, S., Carlson, E., Epstein, C. J., and Cadet, J. L. (1992) Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J. Neurosci. 12, 1658–1667.
Rojas, P. and Rios, C. (1993) Increased striatal lipid peroxidation after intracerebroventricular MPP+ administration to mice. Pharmacol Toxicol. 72, 364–368.
Desole, M. S., Miele, M., Esposito, G., Fresu, L. G., Migheli, R., Zangani, D., Sircana, S., Grella, G., and Miele, E. (1995) Neuronal antioxidant system and MPTP-induced oxidative stress in the striatum and brain stem of the rat. Pharmacol. Biochem. Behay. 51 (4), 581–592.
Desole, M. S., Esposito, G., Fresu, L., Migheli, R., Sircana, S., Delogu, R., Miele, M., and Miele, E. (1996) Further investigation of allopurinol effects of MPTP-induced oxidative stress in the striatum and brain stem of the rat. Pharmacol. Biochem. Behay. 54 (2), 377–383.
Marttila, R. J., Lorentz, H., and Rinne, U. K. (1988) Oxygen toxicity protecting enzymes in Parkinson’s disease: Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus. J. Neurol. Sci. 86, 321–331.
Hirsch, E. C., Graybiel, A. M., and Agid, Y. (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature 334, 345–348.
Ceballos, I., Lafon, M., Javoy-agid, F., et al. (1990) Superoxide dismutase and Parkinson’s disease. Lancet 335, 1035–1036.
Kish, S. J., Morito, C., and Hornykiewicz, O. (1985) Glutathione peroxidase activity in Parkinson’s disease brain. Neurosci. Lett. 58, 343–346.
Perry, T. L., Godin, D. V., and Hansen, S. (1982) Parkinson’s disease: A disorder due to nigral glutathione deficiency? Neurosci. Lett. 33, 305–310.
Perry, T. L., Yong, V. W., Clavier, R. M., Jones, K., Wright, J. M., Foulks, J. G., and Wall, R. A. (1985) Partial protection from the dopaminergic neurotoxin N-methyl-4phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse. Neurosci. Lett. 60, 109–114.
Saggu, H., Cooksey, J., Dexter, D. T., Wells, E. R., Lees, A. J., Jenner, P., and Marsden, C. D. (1989) A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra. J. Neurochem. 53, 692–697.
Poirier, J. Dea, D., Baccichet, A., and Thiffault, C. (1994) Superoxide dismutase expression in Parkinson’s disease. Ann. NY Acad. Sci. 738 116–120.
Parboosingh, J. S., Rousseau, M., Rogan, F., Amit, Z., Chertkow, H., Johnson, W. G., Manganaro, E, Schipper, H. N., Curran, T. J., Stoessl, A. J., and Rouleau, G. A. (1995) Absence of mutations in superoxide dismutase and catalase genes in patients with Parkinson’s disease. Arch. Neurol. 52, 1160–1163.
Poirier, J. and Thiffault, C. (1993) Are free radicals involved in the pathogenesis of idiopathic Parkinson’s disease? Eux Neurol. 33 (Suppl 1), 38–43.
Perry, T. L. and Yong, V. W. (1986) Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra. Neurosci. Lett. 67, 269–274.
Sershen, H., Reith, M. E. A., Hashim, A., and Lajtha, A. (1985) Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity by the antioxidant ascorbic acid. Neuropharmacology 24 (12), 1257–1259.
Wagner, G. C., Jarvis, M. F., and Carelli, R. M. (1985) Ascorbic acid reduces the dopamine depletion induced by MPTP. Neuropharmacology 24 (12), 1261–1262.
Martinovits, G., Melamed, E., Cohen, O., Rosenthal, J., and Uzzan, A. (1986) Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neurosci. Lett. 69, 192–197.
Di Monte, D. A., Sandy, M. S., and Smith, M. T. (1987) Increased efflux rather than oxidation is the mechanism of glutathione depletion by 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP). Biochem. Biophys. Res. Commun. 148, 153–160.
Sershen, H., Debler, E. A., and Lajtha, A. (1987) Effect of ascorbic acid on the synaptosomal uptake of [3H1MPP+, [3H]dopamine, and [14C]GABA. J Neurosci Res, 17, 298–301.
Irwin, I., Wu, E. Y., DeLanney, L. E., Trevor, A. J., and Langston, J. W. (1987) The effect of diethyldithiocarbamate (DDC) on the biodisposition of MPTP: An explanation for enhanced neurotoxicity. Eur. J. of Pharmacol. 141, 209–217.
Nicklas, W. J., Vyas, I., and Heikkila, R. E. (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Life Sci. 36, 2503–2508.
Poirier, J. and Barbeau, A. (1985) 1-Methyl-4-phenyl-pyridinium-induced inhibition of nicotinamide adenosine dinucleotide cytochrome c reductase. Neurosci. Lett. 62, 7–11.
Ramsay, R. R., Krueger, M. J., Youngster, S. K., Gluck, M. R., Casida, J. E., and Singer, T. P. (1991) Interaction of 1-methyl-4-phenylpyridinium ion (MPP+) and its analogs with the rotenone/piericidin binding site of NADH dehydrogenase. J. Neurochem. 56, 1184–1190.
Di Monte, D. A. (1991) Mitochondrial DNA and Parkinson’s disease. Neurology 41 Suppl. 2, 38–42.
Wu, E. Y., Smith, M. T., Bellomo, G., and Di Monte, D. A. (1990) Relationships between the mitochondrial transmembrane potential, ATP concentration, and cytotoxicity in isolated rat hepatocytes. Arch. Biochem. Biophys. 282 (2), 358–362.
Di Monte, D. A., Jewell, S. A., Ekstrom, G., Sandy, M. S., and Smith, M. T. (1986) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) cause rapid ATP depletion in isolated hepatocytes. Biochem. Biophys. Res. Commun. 137(1) 310–315.
Mizuno, Y., Suzuki, K., Sone, N., and Saitoh, T. (1987) Inhibition of ATP synthesis by 1-methyl-4-phenylpyridinium ion (MPP+) in isolated mitochondria from mouse brains. Neurosci. Lett. 81, 204–208.
Kutty, R. K., Santostasi, G., Horng, J., and Krishna, G. (1991) MPTP-induced ATP depletion and cell death in neuroblastoma x glioma hybrid NG 108–15 cells: Protection by glucose and sensitization by tetraphenylborate. Toxicol. Appl. Pharmacol. 107, 377–388.
Di Monte, D. A., Sandy, M. S., Blank, L., and Smith, M. T. (1988) Fructose prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced ATP depletion and toxicity in isolated hepatocytes. Biochem. Biophys. Res. Commun. 153, 734–740.
Chan, P., DeLanney, L. E., Irwin, I., Langston, J. W., and Di Monte, D. A. (1991) Rapid ATP loss caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse brain. J. Neurochem. 57, 348–351.
Chan, P., DeLanney, L. E., Irwin, I., Langston, J. W., and Di Monte, D. A. (1992) MPTP-induced ATP loss in mouse brain. Ann. NYAcad. Sci. 648, 306–308.
Storey, E., Hyman, B. T., Jenkins, B., Brouillet, E., Miller, J. M., Rosen, B. R., and Beal, M. F. (1992) 1-Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. J. Neurochem. 58, 1975–1978.
Chan, P., Langston, J. W., Irwin, I., DeLanney, L. E., and Di Monte, D. A. (1993) 2-Deoxyglucose enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced ATP loss in the mouse brain. J. Neurochem. 61, 610–616.
Mizuno, Y., Saitoh, T., and Sone, N. (1987) Inhibition of mitochondrial alphaketoglutarate dehydrogenase by 1-methyl-4-phenylpyridinium ion. Biochem. Biophys. Res. Commun. 143 (3), 971–976.
Mizuno, Y., Matuda, S., Yoshino, H., Mori, H., Hattori, N., and Ikebe, S. (1994) An immunohistochemical study on alpha-ketoglutarate dehydrogenase complex in Parkinson’s disease. Ann. Neurol. 35, 204–210.
Hornsby, P. J. (1989) Parkinson’s disease, vitamin E, and mitochondrial energy metabolism. Arch. Neurol. 46, 840–841.
Bindoff, L. A., Birch-Machin, M. A., Cartlidge, N. E. R, Parker, W. D., Jr., and Turnbull, D. M. (1991) Respiratory chain abnormalities in skeletal muscle from patients with Parkinson’s disease. J. Neurol. Sci. 104, 203–208.
Hattori, K., Tanaka, M., Sugiyama, S., Obayashi, T., Ito, T., Satake, T., Hanaki, Y., Asai, J., Nagano, M., and Ozawa, T. (1991) Age-dependent increase in deleted mitochondrial DNA in the human heart: Possible contributory factor to presbycardia. Am. Heart J. 121, 1735–1742.
Boyson, S. J. (1991) Parkinson’s disease and the electron transport chain. Ann. Neurol. 30, 330–331.
Parker, W. D., Jr. (1991) Preclinical detection of Parkinson’s disease: Biochemical approaches. Neurology 41 Suppl. 2, 34–36.
Krige, D., Carroll, M. T., Cooper, J. M., Marsden, C. D., and Schapira, A. H. V. (1992) Platelet mitochondrial function in Parkinson’s disease. Ann. Neurol. 32, 782–788.
Nakagawa-Hattori, Y., Yoshino, H., Kondo, T., Mizuno, Y., and Horai, S. (1992) Is Parkinson’s disease a mitochondrial disorder. J. Neurol. Sci. 107, 29–33.
Schapira, A. H. V., Mann, V. M., Cooper, J. M., Drige, D., Jenner, P. J., and Marsden, C. D. (1992) Mitochondrial function in Parkinson’s disease. Ann. Neruol. 32, 5116 — S124.
Shoffner, J. M. and Wallace, D. C. (1992) Heart disease and mitochondrial DNA mutations. Heart Dis. Stroke 1, 235–241.
Wallace, D. C., Shoffner, J. M., Watts, R. L., Juncos, J. L., and Torroni, A. (1992) Mitochondrial oxidative phosphorylation defects in Parkinson’s disease. Ann. Neurol. 32, 113, 114.
Yoshino, H., Nakagawa-Hattori, Y., Kondo, T., and Mizuno, Y. (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson’s disease. J. Neural Transm. Park. Dis. Dement. Sect. 4, 27–34.
Benecke, R., Strümper, P., and Weiss, H. (1993) Electron transfer complexes I and IV of platelets are abnormal in Parkinson’s disease but normal in Parkinson-plus syndromes. Brain 116, 1451–1463.
Cardellach, F., Marti, M. J., Fernandez-Sola, J., Marin, C., Hoek, J. B., Tolosa, E., and Urbano-Marquez, A. (1993) Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson’s disease. Neurology 43, 2258–2262.
Blin, O., Desnuelle, C., Rascol, O., Borg, M., Peyro Saint Paul, H., Azulay, J. P., Bill, F., Figarella, D., Coulom, F., Pellissier, J. F., Montastruc, J. L., Chatel, M., and Serra-trice, G. (1994) Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson’s disease and multiple system atrophy. J. Neurol. Sci. 125, 95–101.
Haas, R. H., Nasirian, F., Nakano, K., Ward, D., Pay, M., Hill, R., and Shults, C. W. (1995) Low platelet mitochondrial Complex I and Complex II/III activity in early untreated Parkinson’s disease. Ann. Neurol. 37, 714–722.
Burkhardt, C., Kelly, J. P., Lim, Y. H., Filley, C. M., and Parker, W. D., Jr. (1993) Neuroleptic medications inhibit complex I of the electron transport chain. Ann. Neurol. 33, 512–517.
Przedborski, S., Jackson-Lewis, V., Muthane, U., Jiang, H., Ferreira, M., Naini, A. B., and Fahn, S. (1993) Chronic levodopa administration alters cerebral mitochondrial respiratory chain activity. Ann. Neurol. 34, 715–723.
Ikebe, S., Tanaka, M., Ohno, K., Sato, W., Hattori, K., Kondo, T., Mizuno, Y., and Ozawa, T. (1990) Increase of deleted mitochondrial DNA in the striatum in Parkinson’s disease and senescence. Biochem. Biophys. Res. Commun. 170, 1044–1048.
Lestienne, P., Nelson, J., Riederer, P., Jellinger, K. A., and Reichmann, H. (1990) Normal mitochondrial genome in brain from patients with Parkinson’s disease and complex I defect. J. Neurochem. 55, 1810–1812.
Cortopassi, G. A. and Arnheim, N. (1990) Detection of a specific mitochondrial DNA deletion in tissues of older humans. Nucleic Acids Res. 18 (23), 6927–6933.
Ozawa, T., Tanaka, M., Ino, H., Ohno, K., Sano, T., Wada, Y., Yoneda, M., Tanno, Y., Miyatake, T., Tanaka, T., Itoyama, S., Ikebe, S., Hattori, N., and Mizuno, Y. (1991) Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson’s disease. Biochem. Biophys. Res. Commun. 176, 938–946.
Ikebe, S., Tanaka, M., and Ozawa, T. (1995) Point mutations of mitochondrial genome in Parkinson’s disease. Mol. Brain Res. 28, 281–295.
Lucking, C. B., Kosel, S., Mehraein, P., and Graeber, M. B. (1995) Absence of the mitochondria] A7237T mutation in Parkinson’s disease. Biochem. Biophys. Res. Commun. 211 (2), 700–704.
Swerdlow, R. H., Parks, J. K., Miller, S. W., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P, Bennett, J. P., Jr., Davis, R. E., and Parker, W. D., Jr. (1996) Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann. Neurol. 40, 663–671.
Chien, K. R., Pfau, R. G., and Farber, J. L. (1979) Ischemic myocardial cell injury. Prevention by chlorpromazine of an accelerated phospholipid degradation and associated membrane dysfunction. Am. J. Pathol. 97, 505–530.
Kass, G. E. N., Wright, J. M., Nicotera, P., and Orrenius, S. (1988) The mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity: role of intracellular calcium. Arch. Biochem. Biophys. 260, 789–797.
Sun, C. J., Johannessen, J. N., Gessner, W., Namura, I., Singhaniyom, W., Brossi, A., and Chiueh, C. C. (1988) Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP+. J. Neural Transm. 74, 75–86.
Cappelletti, G., Brambilla, E., Maci, R., and Camatini, M. (1991) N-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) induced cytoskeletal alterations on “Swiss 3T3” mouse fibroblasts. Neurosci. Lett. 129, 149–152.
Urani, C., Brambilla, E., Santagostino, A., and Camatini, M. (1994) 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) affects the actin cytoskeleton and calcium level of Swiss 3T3 mouse fibroblasts. Toxicology 91, 117–126.
Yamada, T., McGeer, P. L., Baimbridge, K. G., and McGeer, E. G. (1990) Relative sparing in Parkinson’s disease of substantia nigra dopamine neurons containing calbindin-D28K. Brain Res. 526, 303–307.
German, D. C., Manaye, K. F., Sonsalla, P. K., and Brooks, B. A. (1992) Midbrain dopaminergic cell loss in Parkinson’s disease and MPTP-induced Parkinsonism: Sparing of calbindin-D28k-containing cells. Ann. NYAcad. Sci. 648, 42–62.
Hirsch, E. C., Mouatt, A., Thomasset, M., Javoy-Agid, F., Agid, Y., and Graybiel, A. M. (1992) Expression of calbindin D28K-like immunoreactivity in catecholaminergic cell groups of the human midbrain: normal distribution and distribution in Parkinson’s disease. Neurodegeneration 1, 83–93.
Sonsalla, P. K., Nicklas, W. J., and Heikkila, R. E. (1989) Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity. Science 243, 398–400.
Finnegan, K. T., Skratt, J. J., Irwin, I., and Langston, J. W. (1990) The N-methyl-Daspartate (NMDA) receptor antagonist, dextrorphan, prevents the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats. Neurosci. Lett. 105, 300–306.
Whetsell, W. O., Jr. (1997) Current concepts of excitotoxicity. J. Neuropathol. Exp. Neurol. 55, 1–13.
Sonsalla, P. K., Zeevalk, G. D., Manzino, L., Giovanni, A., and Nicklas, W. J. (1992) MK-801 fails to protect against the dopaminergic neuropathology produced by systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice or intranigral 1-methyl-4phenylpyridinium in rats. J. Neurochem. 58, 1979–1982.
Carboni, S., Melis, F., Pani, L., Hadjiconstantinou, M., and Rossetti, Z. L. (1990) The non-competitive NMDA-receptor antagonist MK-801 prevents the massive release of glutamate and aspartate from rat striatum induced by 1-methyl-4-phenylpyridinium (MPP+). Neurosci. Lett. 117, 129–133.
Turski, L., Bressler, K., Rettig, K.-J., Ls’ schmann, P.-A., and Wachtel, H. (1991) Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. Nature 349, 414–418.
Zuddas, A., Vaglini, E, Fornai, F., Fascetti, E, and Corsini, G. U. (1991) MK-801 prevents MPTP-induced nigrostriatal neuronal death in monkeys and mice [Abstract]. Soc. Neurosci. 17 (1), 716.
Srivastava, R., Brouillet, E., Beal, M. F., Storey, E., and Hyman, B. T. (1993) Blockade of 1-methyl-4-phenylpyridinium ion (MPP+) nigral toxicity in the rat by prior decortication or MK-801 treatment: A stereological estimate of neuronal loss. Neurobiol. Aging 14, 295–301.
Tabatabaei, A., Perry, T. L., Hansen, S., and Krieger, C. (1992) Partial protective effect of MK-801 on MPTP-induced reduction of striatal dopamine in mice. Neurosci. Lett. 141, 192–194.
Brouillet, E. and Beal, M. E (1993) NMDA antagonists partially protect against MPTP induced neurotoxicity in mice. Neuroreport 4, 387–390.
Sawada, H., Shimohama, S., Tamura, Y., Kawamura, T., Akaike, A., and Kimura, J. (1996) Methylphenylpyridinium ion (MPP+) enhances glutamate-induced cytotoxicity against dopaminergic neurons in cultured rat mesencephalon. J. Neurosci. Res. 43, 55–62.
Kupsch, A., Ls schmann, P.-A., Sauer, H., Arnold, G., Renner, P., Pufal, D., Burg, M., Wachtel, H., Ten Bruggencate, G., and Oertel, W. H. (1992) Do NMDA receptor antagonists protect against MPTP—toxicity? Biochemical and immunocytochemical analyses in black mice. Brain Res. 592, 74–83.
Michel, P. P. and Agid, Y. (1992) The glutamate antagonist, MK-801, does not prevent dopaminergic cell death induced by the 1-methyl-4-phenylpyridinium ion (MPP+) in rat dissociated mesencephalic cultures. Brain Res. 597, 233–240.
Finiels-Marlier, F., Marini, A. M., Williams, P., and Paul, S. M. (1993) The N-methyl-D-aspartate antagonist MK-801 fails to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium toxicity in vitro. J. Neurochem. 60, 1968–1971.
Chan, P., Di Monte, D. A., and Langston, J. W. (1994) Effects of 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) on levels of glutamate and aspartate in the mouse brain. Brain Res. 647, 249–254.
Chan, P., Langston, J. W., and Di Monte, D. A. (1993) MK-801 temporarily prevents MPTP-induced acute dopamine depletion and MPP+ elimination in the mouse striatum. J. Pharmacol. Exp. Ther. 267, 1515–1520.
Clarke, P. B. S. and Reuben, M. (1995) Inhibition by dizocilpine (MK-801) of striatal dopamine release induced by MPTP and MPP+: possible action at the dopamine transporter. BE J. Pharmacol. 114, 315–322.
Vaglini, F., Fascetti, F., Fornai, F., Maggio, R., and Corsini, G. U. (1994) (+)MK-801 prevents the DDC-induced enhancement of MPTP toxicity in mice. Brain Res. 668, 194–203.
Jarvis, M. F. and Wagner, G. C. (1985) Age-dependent effects of l-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP). Neuropharmacology 24, 581–583.
Irwin, I., Finnegan, K. T., DeLanney, L. E., Di Monte, D. A., and Langston, J. W. (1992) The relationships between aging, monoamine oxidase, striatal dopamine and the effects of MPTP in C57BL/6 mice: A critical reassessment. Brain Res. 572, 224–231.
Date, I., Felten, D. L., and Felten, S. Y. (1990) Long-term effect of MPTP in the mouse brain in relation to aging: Neurochemical and immunocytochemical analysis. Brain Res. 519, 266–276.
Hornykiewicz, O. (1982) Imbalance of brain monoamines and clinical disorders, in Progress in Brain Research, vol. 55, Chemical Transmission in the Brain: The Role of Amines, Amino Acids and Peptides (Buijs, R. M., Pevet, P., and Swaab, D. F., eds.), Elsevier Biomedical, Amsterdam, pp. 419–429.
Benedetti, M. S. and Keane, P. E. (1980) Differential changes in monoamine oxidase A and B activity in the aging rat brain. J. Neurochem. 35, 1026–1032.
Langston, J. W., Irwin, I., and DeLanney, L. E. (1987) The biotransformation of MPTP and disposition of MPP+: The effects of aging. Life Sci. 40, 749–754.
Irwin, I., Delanney, L. E., and Langston, J. W. (1992) Studies in the C57BL/6 mouse, in Advances in Neurology, vol. 60, Parkinson’s Disease: From Basic Research to Treatment. Proceedings of the 10th International Symposium on Parkinson’s Disease (Narabayashi, H., Nagatsu, T., Yanagisawa, N., and Mizuno, Y., eds.), ( Raven, New York, pp. 197–206.
Irwin, I., DeLanney, L. E., McNeill, T. H., Chan, P., Forno, L. S., Murphy, G. M., Jr., Di Monte, D. A., Sandy, M. S., and Langston, J. W. (1994) Aging and the nigrostriatal dopamine system: a non-human primate study. Neurodegeneration 3, 251–265.
Rose, S. P., Nomoto, M., Jackson, E. A., Gibb, W. R. G., Jaehnig, P., Jenner, P., and Marsden, C. D. (1993) Age-related effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets. Eur. J. Pharmacol. 230, 177–185.
Langston, J. W., Irwin, I., Forno, L. S., and DeLanney, L. E. (1987) Parkinson’s disease, aging, and MPTP: clinical and experimental observations, in Recent Developments in Parkinson’s Disease ( Fahn, S., Marsden, C. D., Goldstein, M., and Calne, D. B., eds.), MacMillan Healthcare Information, Florham Park, NJ, pp. 59–74.
Irwin, I. DeLanney, L. E., Chan, P., Sandy, M. S., Di Monte, D. A., and Langston, J. W. (1997) Nigrostriatal monoamine oxidase A and B in aging squirrel monkeys and C57BL/6 mice. Neurobiol. Aging in press.
Fowler, C. J., Wilberg, A., Oreland, L., Marcusson, J., and Winblad, B. (1980) The effect of age on the activity and molecular properties of human brain monoamine oxidase. J. Neural Transm. 49, 1–20.
Gottfries, C. G. (1987) Pharmacology of mental aging and dementia disorders. Clin. Neuropharm. 10 (4), 313–329.
Gottfries, C. G. (1990) Neurochemical aspects on aging and diseases with cognitive impairment. J. Neurosci. Res. 27, 541–547.
Robinson, D. S., Davis, J. M., Nies, A., Ravaris, C. L., and Sylwester, D. (1971) Relation of sex and aging to monoamine oxidase activity of human Brain plasma, and platelets. Arch. Gen. Psychiatry 24, 536–539.
Grote, S. S., Moses, S. G., Robins, E., Hudgens, R. W., and Croninger, A. B. (1974) A stuy of selected catecholamine metabolizing enzymes: a comparison of depressive suicides and alcoholic suicides with controls. J. Neurochem. 23, 791–802.
Shih, J. C. (1975) Multiple forms of monoamine oxidase and aging, in: Aging, vol. 1, ( Brody, H., Harman, D., and Ordy, J. M., eds.), Raven, New York, pp. 191–198.
Cote, L. J. and Kremzner, L. T. (1983) Biochemical changes in normal aging in human brain, in The Dementias ( Mayeux, R. and Rosen, W. G., eds.), Raven, New York, pp. 19–30.
Samorajski, T. and Rolsten, C. (1973) Age and regional differences in the chemical composition of brains of mice, monkeys and humans, in Progress in Brain Research, vol. 40, (Ford, D. H., eds.), Elsevier Science Publishing, Amsterdam, pp. 253–265.
Fowler, J. S., MacGregor, R. R., Wolf, A. P., Arnett, C. D., Dewey, S. L., Schlyer, D., Christman, D., Logan, J., Smith, M., Sachs, H., Aquilonius, S. M., Bjurling, P., Halldin, C., Hartvig, P., Leenders, K. L., Lundquist, H., Oreland, L., Stalnacke, C. G., and Langstrom, B. (1987) Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET. Science 235, 481–485.
Fowler, J. S., Volkow, N. D., Wang, G. J., Pappas, N., Logan, J., MacGregor, R., Alex-off, D., Shea, C., Schlyer, D., Wolf, A. P., Warner, D., Zezulkova, I., and Cilento, R. (1996) Inhibition of monoamine oxidase in the brains of smokers. Nature 379, 733–736.
Ricaurte, G. A., DeLanney, L. E., Irwin, I. and Langston, J. W. (1987) Older dopaminergic neurons do not recover from the effects of MPTP. Neuropharmacology 26(1) 97–99.
Shigenaga, M. K., Hagen, T. M., and Ames, B. N. (1994) Oxidative damage and mitochondrial decay in aging. Proc. Natl. Acad. Sci. 91, 10,771–10, 778.
Desai, V. G., Feuers, R. J., Hart, R. W., and Ali, S. F. (1996) MPP+-induced neurotoxicity in mouse is age-dependent: evidenced by the selective inhibition of complexes of elctron transport. Brain Res. 715, 1–8.
Stuehr, D. J., Kwon, N. S., Nathan, C. F., and Griffith, O. W. (1991) Nw-hydroxy-Larginine is an intermedite in the biosynthesis of nitric oxide from L-arginine. J. Biol. Chem. 266, 6259–6263.
Marietta, M. A. (1993) Nitric oxide synthase structure and mechanism. J. Biol. Chem. 268(17), 12,231–12, 234.
Bredt, D. S. and Snyder, S. H. (1990) Isolation ofnitric oxide synthetase, a calmodulinrequiring enzyme. Proc. Natl. Acad. Sci. USA 87, 682–685.
Babbedge, R. C., Bland-Ward, P. A., Hart, S. L., and Moore, R. K. (1993) Inhibition of rat cerebellar nitric oxide synthase by 7-nitro indazole and related substituted indazoles. Br. J. Pharmacol. 110, 225–228.
Schulz, J. B., Matthews, R. T., Muqit, M. M. K., Browne, S. E., and Beal, M. F. (1995) Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTPinduced neurotoxicity in mice. J. Neurochem. 64, 936–939.
Przedborski, S., Jackson-Lewis, V., Yokoyama, R., Shibata, T., Dawson, V. L., and Dawson, T. M. (1996) Role of neuronal nitric oxide in 1-methy1–4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Proc. Natl. Acad. Sci. USA 93, 4565–4571.
Hantraye, P., Brouillet, E., Ferrante, R. J., Palfi, S., Dolan, R., Matthews, R. T., and Beal, M. E (1996) inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nature Med. 2, 1017–1021.
Cassina, A. and Radi, R. (1996) Differential inhibitory action of nitric oxide and peroxynitrite onb mitochondrial electron transport. Arch. Biochem. Biophys. 328, 309–316.
Lizasoain, I., Moro, M. A., Knowles, R. G., Darley-Usmar, V., and Moncada, S. (1996) Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose. Biochem. J. 314, 877–880.
Stadler, J., Billiar, T. R., Curran, R. D., Stuehr, D. J., Ochoa, J. B., and Simmons, R. L. (1991) Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes. Am. J. Physiol. 260, C910–0916.
Radi, R., Rodriguez, M., Castro, L., and Telleri, R. (1994) Inhibition of mitochondrial electron transport by peroxynitrite. Arch. Biochem. Biophys. 308 (1), 89–95.
Huie, R. E. and Padmaja, S. (1993) The reaction of NO with superoxide. Free Radical Res. Commun. 18, 195–199.
Castagnoli, K., Palmer, S., Anderson, A., Bueters, T., and Castagnoli, N., Jr. (1997) The neuronal nitric oxide synthase inhibitor 7-nitroindazole also inhibits the monoamine oxidase-B catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Chem. Res. Toxicol. 10, 364–368.
b. Di Monte, D. A., Royland, J. E., Anderson, A., Castagnoli, K., Castagnoli, N., Jr., and Langston, J. W. (1997) Inhibition of monoamine oxidase contributes to the protective effect of 7-nitroindazole against MPTP neurotoxicity. J. Neurochem. in press.
Oppenheim, R. W. (1991) Cell death during development of the nervous system. Ann. Rev. Neurosci. 14, 453–501.
McDonald, H. R. and Lees, R. K. (1990) Programmed cell death of autoreactive thymocytes. Nature 343, 642–644.
Mochizuki, H., Goto, K., Mori, H., and Mizuno, Y. (1996) Histochemical detection of apoptosis in Parkinson’s disease. J. Neurol. Sci. 137, 120–123.
Mochizuki, H., Nakamura, N., Nishi, K., and Mizuno, Y. (1994) Apoptosis is induced by 1-methyl-4-phenylpyridinium ion (MPP+) in ventral mesencephalic-striatal co-culture in rat. Neurosci. Lett. 170, 191–194.
Dipasquale, B., Marini, A. M., and Youle, R. J. (1991) Apoptosis and DNA degradation induced by 1-methyl-4-phenylpyridinium in neurons. Biochem. Biophys. Res. Commun. 181, 1442–1448.
Jackson-Lewis, V., Jakowec, M. W., Burke, R. E., and Przedborski, S. (1995) Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurodegeneration 4, 257–269.
Janson, A. M. (1996) Neuronal cell death by apoptosis in vivo in the 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). Soc. Neurosci. Abstracts 22, 721.
Mochizuki, H., Goto, K., Mori, H., and Mizuno, Y., (1996) Histochemical detection of apoptosis in Parkinson’s disease. J. Neurol. Sci. 137, 120–123.
Dragunow, M., Faull, L. M., Lawlor, P., Beilharz, E. J., Singleton, K., Walker, E. B., and Mee, E. (1995) In situ evidence for DNA fragmentation in Huntington’s disease striatum amd Alzheimer’s disease temporal lobe. Neuroreport 6, 1053–1057.
Levi-Montalci, R. (1987) The nerve growth factor 35 years later. Science 237, 1154–1162.
Knusel, B., Michel, P. P., Schwaber, J. S., and Hefti, F. (1990) Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. J. Neurosci. 10 (2), 558–570.
Knusel, B., Winslow, W., Rosenthal, A., Burton., L. E., Seid, D. D., Nickolics, K., and Hefti, F. (1991) Promotion of central cholinergic and dopaminergic neuron differentiation by brain derived neurotrophic factor but not neurotrophin-3. Proc. Natl. Acad. Sci. USA 88, 961–965.
Hyman, C., Hofer, M., Barde, Y. A., Juhasz, M., Yancopoulos, G. D., Squinto, S. P., and Lindsay, R. M. (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350, 230–232.
Spina, M. B., Squinto, S. P., Miller, J., Lindsay, R. M., and Hyman, C. (1992) Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: Involvement of the glutathione system. J. Neurochem. 59, 99–106.
Garcia, E., Rios, C., and Sotelo, J. (1992) Ventricular injection of nerve growth factor increases dopamine content in the striata of MPTP-treated mice. Neurochem. Res. 17, 979–982.
Glass, D. J. and Yancopoulos, G. D. (1993) The neurotrophins and their receptors. Trends Cell. Biol. 3, 262–268.
Beck, K. D., Knusel, B., and Hefti, F. (1993) The nature of the trophic action of brain-derived neurotrophic factor, des(1–3)-insulin-like growth factor-1, and basic fibroblast growth factor on mesencephalic dopaminergic neurons developing in culture. Neuroscience 52 (4), 855–866.
Frim, D. M., Uhler, T. A., Galpern, W. R., Beal, M. F., Breakefield, X. O., and Isacson, O. (1994) Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc. Natl. Acad. Sci. USA 91, 5104–5108.
Tsukahara, T., Takeda, M., Shimohama, S., Ohara, O., and Hashimoto, N. (1995) Effects of brain-derived neurotrophic factor on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induce parkinsonsim in monkeys. Neurosurgery 37 (4), 733–741.
Hyman, C., Juhasz, M., Jackson, C., Radziejewski, C., and Linsay, R. M. (1991) Effects of BDNF and NT-3 on dopaminergic and GABAergic neurons of the ventral mesencephalon. Soc. Neurosci. Abstracts 17, 908.
Hyman, C., Juhasz, M., Jackson, C., Wright, P., Ip, N. Y., and Lindsay, R. M. (1994) Overlapping and distinct actions of the neurotrophins, BDNF, NT-3, and NT-4/5, on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. J. Neurosci. 14, 335–347.
Kirschner, P. B., Jenkins, B. G., Schulz, J. B., Finkelstein, S. P., Matthews, R. T., Rosen, B. R., and Beal, M. E (1996) NGF, BDNF and NT-5, but not NT-3 protect against MPP+ toxicity and oxidative stress in neonatal animals. Brain Res. 713, 178–185.
Jackson, G. R., Apffel, L., Werrbach-Perez, K., and Perez-Polo, J. R. (1990) Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. I. Stimulation of hydrogen peroxide resistance. J. Neurosci. Res. 25, 360–368.
Pan, Z. and Perez-Polo, J. R. (1993) Role of nerve growth factor in oxidant homeostasis: glutathione metabolism. J. Neurochem. 61, 1713–1721.
Nistico, G., Cirolo, M. R., Fishkin, K., Iannone, M., De Martino, A., and Rotilio, G. (1992) NGF restores decrease in catalase activity and increases superoxide dismutase and glutathione peroxidase activity in the brain of aged rats. Free Radical Biol. Med. 12, 177–181.
Hung, H. C. and Lee, E. H. Y. (1996) The mesolimbic dopaminergic pathway is more resistant than the nigrostriatal dopaminergic pathway to MPTP and MPP+ toxicity: role of BDNF gene expression. Mol. Brain Res. 41, 16–26.
Ferrari, G., Minozzi, M. C., Toffano, G., Leon, A., and Skaper, S. D. (1989) Basic fibroblast growth factor promotes the survival and development of mesencephalic neurons in culture. Dev. Biol. 133, 140–147.
Mayer, E., Dunnett, S. B., Pellitteri, R., and Fawcett, J. W. (1993) Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons I. Effects in vitro. Neuroscience 56, 379–388.
Engele, J. and Bohn, M. C. (1991) The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia. J. Neurosci. 11, 3070–3078.
Unsicker, K., Reichert-Preibsch, H., and Wewetzer, K. (1992) Stimulation of neuron-survival by basic FGF and CNTF is a direct effect and not mediated by non-neuronal cells: evidence from single cells cultures. Dev. Brain Res. 65, 285–288.
Date, I., Notter, M. E. D., Felten, S. Y., and Felten, D. L. (1990) MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF). Brain Res. 526, 156–160.
Otto, D. and Unsicker, K. (1990) Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J. Neurosci. 10, 1912–1921.
Farris, T. W., DiStefano, L., and Schneider, J. S. (1994) Intranigral infusion of CNTF, but not bFGF, EGF or TGFbl, restores striatal DOPAC but not dopamine levels in MPTP-treated mice. Soc. Neurosci. Abstracts 20, 1646.
Jin, B. K. and Iacovitti, L. (1996) Dopamine differentiation factors increase striatal dopaminergic function on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice. J. Neurosci. Res. 43, 331–334.
Du, X. Y., Stull, N. D., and Iacovitti, L. (1994) Novel expression of the tyrosine hydroxylase gene requires both acidic fibroblast growth factor and an activator. J. Neurosci. 14, 7688–7694.
Hoffer, B. J., Hoffmann, A., Bowenkamp, K., Huettl, R, Hudson, J., Martin, D., Lin, L. F. H., and Gerhardt, G. A. (1994) Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo. Neurosci. Lett. 182, 107–111.
Tomac, A., Lindqvist, E., Lin, L. F. H., Ogren, S. O., Young, D., Hoffer, B. J., and Olson, L. (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373, 335–339.
Hou, J. G. G., Lin, L. F. H., and Mytilineou, C. (1996) Glial cell line-derived neurotrophic factor exerts neurotrophic effects on dopaminergic neurons in itro and promotes their survival and regrowth after damage by 1-methyl-4-phenylpyridinium. J. Neurochem. 66, 74–82.
Zeng, B. Y., Jenner, P., and Marsden, C. D. (1996) Altered motor function and graft survival produced by basic fibroblast growth factor in rats with 6-OHDA lesions and fetal ventral mesencephalic grafts are associated with glial proliferation. Exp. Neurol. 139, 214–226.
Wang, J., Bankiewicz, K. S., Plunkett, R. J., and Oldfield, E. H. (1994) Intrastriatal implantation of interleukin-1 Reduction of parkinsonism in rats by enhancing neuronal sprouting from residual dopaminergic neurons in the ventral tegmental area of the midbrain. J. Neurosurg. 80, 484–490.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Royland, J.E., Langston, J.W. (1998). MPTP. In: Kostrzewa, R.M. (eds) Highly Selective Neurotoxins. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-477-1_6
Download citation
DOI: https://doi.org/10.1007/978-1-59259-477-1_6
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-047-2
Online ISBN: 978-1-59259-477-1
eBook Packages: Springer Book Archive