Are Dopamine, Norepinephrine, and Serotonin Precursors of Biologically Reactive Intermediates Involved in the Pathogenesis of Neurodegenerative Brain Disorders?

  • Glenn Dryhurst
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 500)

Abstract

During the past two or three decades an immense amount of research has been carried out to understand the fundamental molecular mechanisms that underlie the neurotoxicity evoked by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), methamphetamine (MA) and related amphetamine drugs of abuse. The neurotoxicity of MPTP is of particular interest because it not only mimics the symptoms and major pathobiochemical changes that occur in Parkinson’s disease (PD) but also arguably provides the best model of PD in animals (Gerlach et al.,1991; Gerlach and Riederer, 1996; Royland and Langston, 1998). Interest in the neurotoxicity evoked by MA derives not only from the fact that this compound is a widely abused psychoactive drug but in animals it also mimics many of the major pathobiochemical changes that occur in PD (Gerlach and Riederer, 1996) although it is a less selective neurotoxin than MPTP. Transient cerebral ischemia, or ischemia-reperfusion (I-R), can also lead to neurodegeneration although this is even less selective than MA. Nevertheless, there are a rather striking number of similar factors that appear to be key steps in a complex cascade of processes that compromise the neurotoxic mechanisms evoked by MPTP, MA and I-R. In this communication similarities associated with the neurotoxicity evoked by MPTP, MA and I-R will be briefly reviewed. Subsequently, these will be integrated into a working hypothesis for the underlying neurotoxic mechanisms in which one or more of the neurotransmitters dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT; serotonin) are proposed to be the precursors of biologically reactive intermediates in the pathological processes.

Keywords

Superoxide Respiration Neurol Nash Sulfhydryl 

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References

  1. Albers, D.S., Zeevalk, G.D., and Sonsalla, P.K., 1996, Damage to dopaminergic nerve terminals in mice by combined treatment of intrastriatal malonate with systemic methampehtamine or MPTP. Brain Res. 718: 217–220.PubMedCrossRefGoogle Scholar
  2. Ali, S.F., and Itzhak, Y., 1998, Effects of 7-nitroindazole, an nNOS inhibitor, on methamphetamine-induced dopaminergic and serotonergic neurotoxicity in mice. Ann. N.Y. Acad. Sci. 844: 122–130.PubMedCrossRefGoogle Scholar
  3. Andén, N.-E., Fuxe, B., Hamberger, B. and Hökfelt, T., 1966, A quantitative study on the nigro-neostriatal dopamine neuron system in the rat. Acta Physiol. Scand. 67: 306–312.PubMedCrossRefGoogle Scholar
  4. Ara, J., Przedborski, S., Naini, A.B., Jackson-Lewis, V., Trifiletti, R.R., Horwitz, J., and Ischiropoulos, H. 1998, Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Proc. Nat. Acad. Sci. U.S.A. 95: 7659–7663.CrossRefGoogle Scholar
  5. Axt, K.J., and Molliver, M.E., 1991, Immunocytochemical evidence for methamphetamine-induced serotonergic axon loss in the rat brain. Synapse 9: 302–313.PubMedCrossRefGoogle Scholar
  6. Beal, M.F., 1995 Mitochondrial Dysfunction and Oxidative Damage in Neurodegenerative Diseases R.G. Landes Co., Austin, TX.Google Scholar
  7. Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N., 1984, Elevation of extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neurochem. 43: 1369–1374.PubMedCrossRefGoogle Scholar
  8. Berger, U.V., Gu, X.F., and Azmitia, E.C., 1992, The substituted amphetamines 3,4methylenedioxymethamphetamine, methamphetamine, p-chloroamphetamine and fenfluramine induce 5hydroxytrytpamine release via a common mechanism blocked by fluoxetine and cocaine. Eur. J. Pharmacol. 215: 153–160.PubMedCrossRefGoogle Scholar
  9. Berman, S.B., and Hastings, T.G., 1999, Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson’s disease. J. Neurochem. 73: 1127–1137.PubMedCrossRefGoogle Scholar
  10. Bezard, E. Gross, C.E., Fournier, M.C., Dovero, S., Bloch, B., and Jaber, M., 1999, Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter. Exp. Neurol. 155: 268–273.PubMedCrossRefGoogle Scholar
  11. Blass, J.P., Sheu, R.K., and Gibson, G.E., 2000, Inherent abnormalities in energy metabolism in Alzheimer disease. Interaction with cerebrovascular compromise. Ann. N.Y. Acad. Sci. 903: 204–221.PubMedCrossRefGoogle Scholar
  12. Burrows, K.B., Gudelsky, G., Yamamoto, B.K., 2000, Rapid and transient inhibition of mitochondrial function following methamphetamine or 3,4-methylenedioxymethamphetamine administration. Eur. J. Pharmacol. 398: 11–18.PubMedCrossRefGoogle Scholar
  13. Cadet, J.L., Sheng, P., Ali, S., Rothman, R., Carlson, E., and Epstein, C., 1994, Attenuation of methamphetamine-induced neurotoxicity in copper/zinc superoxide dismustase transgenic mice. J. Neurochem. 62: 380–383.PubMedCrossRefGoogle Scholar
  14. Callahan, B. Yuan, J., Stover, G., Hatzidimitriou, G., and Ricaurte, G., 1998, Effects of 2-deoxy-D-glucose on methamphetamine-induced dopamine and serotonin neurotoxicity. J. Neurochem. 70: 190–197.PubMedCrossRefGoogle Scholar
  15. Cao, C.J., Eldefrawi, A.T., and Eldefrawi, M.E., 1990, ATP-regulated neuronal catecholamine uptake: a new mechanism. Life Sci. 47: 655–667.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. Cebers, G., Cebere, A., and Liljequist, S., 1998, Metabolic inhibition potentiates AMPA-induced Ca2+ fluxes and neurotoxicity in rat cerebellar granule cells. Brain Res. 779: 194–204.PubMedCrossRefGoogle Scholar
  18. Chan, P., Delanney, L.E., Irwin, I., Langston, J.W., and Di Monte, D., 1991, Rapid ATP loss caused by MPTP in mouse brain. J. Neurochem 57:348–351.PubMedCrossRefGoogle Scholar
  19. Chan, P., Di Monte, D.A., Luo, J.-J., Delanney, L.E., Irwin, I. and Langston, J.W., 1994, Rapid ATP loss caused by methamphetamine in the mouse striatum: relationship between energy impairment and dopaminergic neurotoxicity. J. Neurochem. 62: 2484–2487.PubMedCrossRefGoogle Scholar
  20. Chiueh, C.C., and Huang, S.J., 1991, MPP+ enhances potassium evoked striatal dopamine release through an 0-conotoxin-insensitive, tetrodotoxin-and nimodipine-sensitive calcium dependent mechanism. Ann. N.Y. Acad. Sci. 635: 393–396.PubMedCrossRefGoogle Scholar
  21. Chiueh, C.C., Wu, R.-M., Mohanakumar, K.P., Sternberger, L.M., Krishna, G., Obata, T., and Murphy, D.L., 1994, In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia. Ann. N.Y. Acad. Sci. 738:25–36.PubMedCrossRefGoogle Scholar
  22. Clemens, J.A., and Phebus, L.A., 1988, Dopamine depletion protects striatal neurons from ischemia-induced cell death. Life Sci. 42: 707–713.PubMedCrossRefGoogle Scholar
  23. Cooper, A.J.L., 1998, Role of astrocytes in maintaining cerebral glutathione homeostasis and in protecting the brain against xenobiotics and oxidative stress, in Glutathione in the Nervous System (C.A. Shaw, Ed.), Taylor and Francis, Washington, D.C., pp. 91–115.Google Scholar
  24. Cooper, J.M., and Schapira, A.H.V., 1997, Mitochondrial dysfunction in neurodegeneration. J. Bioenerg. Biomembr. 29: 175–183.PubMedCrossRefGoogle Scholar
  25. Cooper, A.J.L., Pulsinelli, W.A., and Duffy, T.E., 1980, Glutathione and ascorbate during ischemia and postischemic reperfusion in rat brain. J. Neurochem. 35 1242–1245.PubMedCrossRefGoogle Scholar
  26. Chen, J.-C., Crino, P.B., To, A.C.S., and Volicer, L., 1989, Increased serotonin efflux by a partially oxidized serotonin: tryptamine-4,5-dione. J. Pharmacol. Exp. Therap. 250: 141–148.Google Scholar
  27. Corrigan, F.M., Wienberg, C.L., Shore, R.F., Daniel, S.E., and Mann, D., 2000, Organochlorine insecticides in substantia nigra in Parkinson’s disease. J. Toxicol. Environ. Health 59: 229–234.CrossRefGoogle Scholar
  28. Crino, P.B. Vogt, B.A., Chen, J.-C., and Volicer, L., 1989, Neurotoxic effects of partially oxidized serotonin: tryptamine-4,5-dione. Brain Res. 504: 247–257.PubMedCrossRefGoogle Scholar
  29. Crow, J.P., Spruell, C., Chen, J., Gunn, C., Ischiropoulos, H., Tsai, M., Smith, C.D., Radi, R., Koppenol, W.H., and Beckman, J.S., 1994, On the pH-dependent yield of hydroxyl radical products from peroxynitrite. Free Rad. Biol. Med. 16: 331–338.PubMedCrossRefGoogle Scholar
  30. Della Donne, K.T., and Sonsalla, P.K., 1994, Protection against methamphetamine-induced neurotoxicity to neostriatal dopamine neurons by adenosine receptor activation. J. Pharmacol. Exp. Therap. 271: 1320–1326.Google Scholar
  31. Dexter, D.T., Sian, J., Rose, H. Hindmarsh, J.-G., Mann, V.M., Cooper, J.M., Wells, F.R., Daniel, S.E., Lees, A.J., Schapira, A.H.V., Jenner, P., and Marsden, C.D., 1994, Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann. Neurol. 35: 38–44.PubMedCrossRefGoogle Scholar
  32. Dorrepaal, C.A., van Bel, F., Moison, R.M., Shadid, M., van de Bor, M., Steedijk, P., and Berger, H.M., 1997, Oxidative stress during post-hypoxic-ischemia reperfusion in the newborn lamb: the effect of nitric oxide synthesis inhibition. Pediatr. Res. 41: 321–326.PubMedCrossRefGoogle Scholar
  33. Dringen, R., Pfeiffer, B. and Hamprecht, B. 1999, Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CsyGly as precursor for neuronal glutathione. J. Neurosci. 19: 562–569.PubMedGoogle Scholar
  34. Edwards, R.H., 1993, Neural degeneration and the transport of neurotransmitters. Ann. Neurol. 34: 638–645.PubMedCrossRefGoogle Scholar
  35. Eliasson, M.J., Huang, Z., Ferrante, R.J., Sasamata, M., Molliver, S.E., Snyder, S.H., and Moskowitz, M.A., 1999, Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neuronal damage. J. Neurosci. 19: 5910–5918.PubMedGoogle Scholar
  36. Ferrante, R.J., Hantraye, P., Brouillet, E., and Beal, M.F., 1999, Increased nitrotyrosine immunoreactivity in substantia nigra neurons in MPTP treated baboons is blocked by inhibition of neuronal nitric oxide synthase. Brain Res. 823: 177–182.PubMedCrossRefGoogle Scholar
  37. Ferraro, T.N., Golden, G.T., DeMattei, M., Hare, T.A., and Fariello, R.G., 1986, Effect of 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) on levels of glutathione in the extrapyramidal system of the mouse. Neuropharmacology 25: 1071–1074.PubMedCrossRefGoogle Scholar
  38. Fishman, J.B., Rubins, J.B., Chen, J.-C., Dickey, B.F., and Volicer, L., 1991, Modification of brain guanine nucleotide-binding regulatory proteins by tryptamine-4,5-dione, a neurotoxic derivative of serotonin. J. Neurochem. 56, 1851–1854.PubMedCrossRefGoogle Scholar
  39. Fleckenstein, A.E., Beyeler, M.L., Jackson, J.C., Wilkins, D.G., Gibb, J.W., and Hanson, G.R., 1997, Methamphetamine-induced decrease in tryptophan hydroxylase activity: role of 5-hydroxytryptaminergic transporters. Eur. J. Pharmacol. 324:179–186.PubMedCrossRefGoogle Scholar
  40. Flint, D.H., Tuminello, J.F., and Emptage, M.H., 1993, The inactivation of Fe-S cluster containing hydrolyases by superoxide. J. Biot. Chem. 268:22369–22376.Google Scholar
  41. Forman, L.J., Liu, P., Nagele, R.G., Yin, K., and Wong, P.Y., 1998, Augmentation of nitric oxide, superoxide, and peroxynitrite production during cerebral ischemia and reperfusion in the rat. Neurochem. Res. 23: 141–148.PubMedCrossRefGoogle Scholar
  42. Fornstedt, B., Brun, A., Rosengren, E., and Carlsson, A., 1989, The apparent autoxidation rate of catechols in dopamine-rich regions of human brain increases with the degree of depigmentation of substantia nigra. J. Neural Transm. [P-D Dementia Sect.] 1: 279–295.CrossRefGoogle Scholar
  43. Fumagalli, F., Gainetdinov, R.R., Valenzano, K.J., and Caron, M.G., 1998, Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence from mice lacking the transporter. J. Neurosci. 18: 4861–4869.PubMedGoogle Scholar
  44. Fumagalli, F., Gainetdinov, R.R., Wang, Y.M., Valenzano, K.J., Miller, G.W., and Caron, M.G., 1999, Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knockout mice. J. Neurosci. 19: 2424–2431.PubMedGoogle Scholar
  45. Gainetdinov, R.R., Fumagalli, F., Wang, Y.M., Jones, S.R., Levey, A.I., Miller, G.W., and Caron, M.G., 1998, Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J. Neurochem. 70: 1973–1978.PubMedCrossRefGoogle Scholar
  46. Gardner, P.R., Constantino, G., Szabo, C., and Salzman, A.L., 1997, Nitric oxide sensitivity of aconitases. J. Biol. Chem. 272: 25071–25076.PubMedCrossRefGoogle Scholar
  47. Gerlach, M., and Riederer, P., 1996, Animal models of Parkinson’s disease: an empirical comparison with the phenomenology of the disease in man. J.Neural Transm. 103:987–1041.PubMedCrossRefGoogle Scholar
  48. Gerlach, M., Riederer, P., Przuntek, H., and Youdim, M.B.H., 1991, MPTP mechanisms of neurotoxicity and their implications for Parkinson’s disease. Eur. J. Pharmacol. 208: 273–286.PubMedCrossRefGoogle Scholar
  49. Gibb, J.W., Hanson, G.R., and Johnson, M., 1994, Neurochemical mechanisms of toxicity, in: Amphetamine and Its Analogs Psychopharmacology Toxicology and Abuse (A.K. Cho, and D.S. Segal, Eds.), Academic Press, San Diego, pp. 269–289.Google Scholar
  50. Gibb, J.W., Johnson, M., Elayan, I., Lim, H.K., Matsuda, L., and Hanson, G.R., 1997, Neurotoxicity of amphetamines and their metabolites, in Pharmacokinetics Metabolism and Pharmaceutics of Drugs of Abuse (R.S. Rapaka, N. Chiang, and B.R. Martin, Eds.) NIDA Research Monograph 173,pp. 128–145.PubMedGoogle Scholar
  51. Gill, R., Foster, A.C., and Woodruff, G.N., 1988, MK-801 is neuroprotective in gerbils when administered during the post-ischemic period. Neuroscience 25: 847–855.PubMedCrossRefGoogle Scholar
  52. Giovanni, A., Sonsalla, P.K., and Heikkila, R.E., 1994, Studies on species sensitivity to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Part 2. Central administration of 1-methyl-4phenylpyridinium. J. Pharmacol. Exp. Therap. 270: 1008–1014.Google Scholar
  53. Giovanni, A., Liang, L.P., Hastings, T.G., and Zigmond, M.J., 1995, Estimating hydroxyl radical content in rat brain using systemic and intraventricular salicylate: impact of methamphetamine. J. Neurochem. 64: 1819–1825.PubMedCrossRefGoogle Scholar
  54. Globus, M.Y.-T., Busto, R., Dietrich, W.D., Martinez, E., Valdés, I., and Ginsberg, M.D., 1988, Instraischemic extracellular release of dopamine and glutamate is associated with striatal vulnerability to ischemia. Neurosci. Lett. 91: 36–40.PubMedCrossRefGoogle Scholar
  55. Globus, M.Y.-T., Busto, R., Dietrich, W.D., Martinez, E., Valdés, I., and Ginsberg, M.D., 1989, Direct evidence for acute and massive norepinephrine release in the hippocampus during transient ischemia. J. Cereb. Blood Flow Metab. 9: 892–896.PubMedCrossRefGoogle Scholar
  56. Globus, M.Y.-T., Wester, P., Busto, R., and Dietrich, W.D., 1992, Ischemia-induced extracellular release of serotonin plays a role in CAI neuronal death in rats. Stroke 23: 1595–1601.PubMedCrossRefGoogle Scholar
  57. Good, P.F., Olanow, C.W., and Perl, D.P., 1992, Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson’s disease: a LAMMA study. Brain Res. 593: 343–346.PubMedCrossRefGoogle Scholar
  58. Good, P.F., Hsu, A., Werner, P., Perl, D.P., and Olanow, C.W., 1998, Protein nitration in Parkinson’s disease. J. Neuropath. Exp. Neurol. 57: 338–342.PubMedCrossRefGoogle Scholar
  59. Greene, J.G., and Greenamyre, J.T., 1995, Exacerbation of NMDA, AMPA, and L-glutamate excitotoxicity by the succinate dehydrogenase inhibitor malonate. J. Neurochem. 64: 2332–2338.PubMedCrossRefGoogle Scholar
  60. Greene, J.G., and Greenamyre, J.T., 1996, Bioenergetics and excitotoxicity: the weak excitotoxic hypothesis, in Neurodegeneration and Neuroprotection in Parkinson’s Disease (C.W. Olanow, P. Jenner and M. Youdim, Eds.,), Academic Press, New York, pp. 125–142.Google Scholar
  61. Gutteridge, J.M.C., 1996, Hydroxyl radical, iron, oxidative stress, and neurodegeneration. Ann. N.Y. Acad. Sci. 738:201–213.CrossRefGoogle Scholar
  62. Han, J., Cheng, F.-C., Yang, Z., and Dryhurst, G., 1999, Inhibitors of mitochondrial respiration, iron (II), and hydroxyl radical evoke release and extracellular hydrolysis of glutathione in rat striatum and substantia nigra: potential implications to Parkinson’s disease. J. Neurochem. 73:1683–1695.PubMedCrossRefGoogle Scholar
  63. Hardy, J., Adolfsunn, R., Alafuzoff, L., Bucht, G., Marcusson, J., Nyberg, P., Perdahl, E., Wester, P., and Winblad, B., 1985, Transmitter defects in Alzheimer’s disease. Neurochem. Int. 7: 545–563.PubMedCrossRefGoogle Scholar
  64. Heikkila, R.E., Orlansky, H., and Cohen, G., 1975, Studies on the distinction between uptake inhibition and release of (3H) dopamine in rat brain tissue slices. Biochem. Pharmacol. 24: 847–852.PubMedCrossRefGoogle Scholar
  65. Hirabayashi, H., Takizawa, S., Fukuyama, N., Nakazawa, H., and Shinohara, Y., 1999, 7-Nitroindazole attenuates nitrotyrosine formation in the early phase of cerebral ischemia-reperfusion in mice. Neurosci. Lett. 268:111–113.PubMedCrossRefGoogle Scholar
  66. Hirata, H., Landenheim, B., Rothman, R.B. Epstein, C., and Cadet, J.L., 1995, Methamphetamine-induced serotonin neurotoxicity is mediated by superoxide radicals. Brain Res. 677: 345–347.PubMedCrossRefGoogle Scholar
  67. Hochstetler, S.E., Puopolo, M., Gustincich, S., Raviola, E., and Wightman, R.M., 2000, Real-time amperometric measurements of zeptomole quantities of dopamine released from neurons. Anal. Chem. 72: 489–496.PubMedCrossRefGoogle Scholar
  68. Hornykiewicz, O., and Kish, S.J., 1980, Biochemical pathophysiology of Parkinson’s disease. Adv. Neurol. 45: 19–34.Google Scholar
  69. Hotchkiss, A., and Gibb, J.W., 1980, Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase in rat brain. J. Pharmacol. Exp. Therap. 214:257–263.Google Scholar
  70. Huether, G., Zhou, D., and Rüther, E., 1997, Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) and its congeners. J. Neural Transm. 104: 771–794.PubMedCrossRefGoogle Scholar
  71. Ikeda, M., Nakazawa, T., Abe, K., Takeru, K., and Yamatsu, K., 1989, Extracellular accumulation of glutamate in the hippocampus induced by ischemia is not calcium dependent-in vitro and in vivo evidence. Neurosci. Lett. 96:202–206.PubMedCrossRefGoogle Scholar
  72. Imman, S.Z., Crow, J.P., Newport, G.D., Islam, F., Slikker, W., and Ali, S.F., 1999, Methamphetamine generates peroxynitrite and produces dopaminergic neurotoxicity in mice: protective effects of peroxynitrite decomposition catalyst. Brain Res. 837: 15–21.CrossRefGoogle Scholar
  73. 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-4phenylpyridine by dopamine neurons explains selective toxicity. Proc. Nat. Acad. Sci. U.S.A. 82: 2173–2177.CrossRefGoogle Scholar
  74. Jiang, X.-R., Wrona, M.Z., and Dryhurst, G. 1999, Tryptamine-4,5-dione, a putative endotoxic metabolite of the superoxide-mediated oxidation of serotonin, is a mitochondrial toxin: possible implications in neurodegenerative brain disorders. Chem. Res. Toxicol. 12: 429–436.PubMedCrossRefGoogle Scholar
  75. Johnson, M., Hanson, G.R., and Gibb, J.W., 1989, Effect of MK-801 on the decrease in tryptophan hydroxylase induced by methamphetamine and its methylenedioxy analog. Eur. J. Pharmacol. 165 315–318.PubMedCrossRefGoogle Scholar
  76. Kato, H., Araki, T., and Kogure, K., 1990, Role of excitotoxic mechanism in the development of neuronal damage following repeated brief cerebral ischemia in the gerbil: protective effects of MK-801 and pentobarbital. Brain Res. 516: 175–179.PubMedCrossRefGoogle Scholar
  77. Keller, J.N., Kindy, M.S., Holtsberg, F.W., St. Clair, D.K., Yen, H.C., Germeyer, A., Steiner, S.M., Bruce-Keller, A.J., Hutchins, J.B., and Mattson, M.P., 1998, Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation and mitochondrial dysfuction. J. Neurosci. 18: 687–697.PubMedGoogle Scholar
  78. Kerry, N., and Rice-Evans, C., 1999, Inhibition of peroxynitrite-mediated oxidation of dopamine by flavonoid and phenolic antioxidants and their structural relationships. J. Neurochem. 73 247–253.PubMedCrossRefGoogle Scholar
  79. Keyer, K., and Imlay, J.A., 1997, Inactivation of dehydratase [4Fe-4S] clusters and disruption of iron homeostasis upon cell exposure to peroxynitrite. J. Biol. Chem. 272: 27652–27659.PubMedCrossRefGoogle Scholar
  80. Kita, T., Takahashi, M., Kubo, K., Wagner, G.C., and NakashimaT. 1999, Hydroxyl radical formation following methamphetamine administration to rats. Pharmacol. Toxicol. 85: 133–137.PubMedCrossRefGoogle Scholar
  81. Klivenyi, P, St.Clair, D., Wermer, M., Yen, H.C., Oberley, T., Yang, L., and Beal, M.F., 1998, Manganese superoxide dismutase overexpression attenuates MPTP toxicity. Neurobiol. Dis. 5: 253–258.PubMedCrossRefGoogle Scholar
  82. Kobayashi, T., Matsumme, H., Matuda, S., and Mizuno, Y., 1998, Association between the gene encoding the E2 subunit of the a-ketoglutarate dehydrogenase complex and Parkinson’s disease. Ann. Neurol. 43 120–123.PubMedCrossRefGoogle Scholar
  83. Kuhn, D.M., Aretha, C.W., Geddes, T.J., 1999, Peroxynitrite inactivation of tyrosine hydroxylase: mediation by sulfhydryl oxidation, not tyrosine nitration. J. Neurosci. 19: 10289–10294.PubMedGoogle Scholar
  84. Lada, M.W., and Kennedy, R.T., 1997, In vivo monitoring of glutathione and cysteine in rat caudate nucleus using microdialysis on-line with capillary zone electrophoresis-laser induced fluorescence detection. J. Neurosci. Meth. 72: 153–159.CrossRefGoogle Scholar
  85. Lafon-Cazal, M., Pletri, S., Culcasi, M., and Bockaert, J., 1993, NMDA-dependent superoxide production and neurotoxicity. Nature 364: 535–537.PubMedCrossRefGoogle Scholar
  86. Lan, J., and Jiang, D.H., 1997, Desferrioxamine and vitamin E protect against iron and MPTP-induced neurodegeneration in mice. J. Neural Transm. 104: 469–481.Google Scholar
  87. Lancelot, E., Callebert, J., Revaud, M.L., Boulu, R.G., and Plotkine, M., 1995, Detection of hydroxyl radicals in rat striatum during transient focal cerebral ischemia: possible implications in tissue damage. Neurosci. Lett. 197: 85–88.PubMedCrossRefGoogle Scholar
  88. LaVoie, M.J., and Hastings, T.G., 1999, Dopamine quinone formation and protein modification associated with the striatal neurotoxicity of methamphetamine: evidence against a role for extracellular dopamine. J. Neurosci. 19:1484–1491.PubMedGoogle Scholar
  89. Le Couteur, J.M., and McClean, A.J., 1998, The ageing liver: drug clearance and an oxygen diffusion barrier hypothesis. Clin. Pharmacokinetics 34: 359–373.CrossRefGoogle Scholar
  90. Lee, J.-M., Zipfel, G.J., and Choi, D.W., 1999, The changing landscape of ischaemic brain injury mechanisms. Nature 399: A7–A14.PubMedCrossRefGoogle Scholar
  91. Lew, R., Malberg, J.E., Ricaurte, G.A., and Seiden, L.S., 1998, Evidence for and mechanism of action of neurotoxicity of amphetamine related compounds, in Highly Selective Neurotoxins: Basic and Clinical Applications (R.M., Kostrzewa, Ed.), Humana Press, Totowa, N.J., pp. 235–268.Google Scholar
  92. Li, H. and Dryhurst, G., 1997, Irreversible inhibition of mitochondrial complex I by 7-(2-aminoethyl)-3,4dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1): a putative nigral endotoxin of relevance to Parkinson’s disease. J. Neurochem. 69: 1530–1541.PubMedCrossRefGoogle Scholar
  93. Li, H., Shen, X.-M., and Dryhurst, G., 1998, Brain mitochondria catalyze the oxidation of 7-(2-aminoethyl)3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid to intermediates that irreversibly inhibit complex I and scavenge glutathione: potential relevance to the pathogenesis of Parkinson’s disease. J. Neurochem. 71:2049–2062.PubMedCrossRefGoogle Scholar
  94. Li, X., Wallin, C., Weber, S.G., and Sandberg, M., 1999, Net efflux of cysteine, glutathione and related metabolites form rat hippocampal slices during oxygen/glucose deprivation: dependence on ‘y-glutamyl transpeptidase. Brain Res.815: 81–88.PubMedCrossRefGoogle Scholar
  95. Loschmann, P.A., Lange, K.W., Wachtel, H., and Turski, L., 1994, MPTP-induced degeneration: interference with glutamatergic toxicity. J. Neural Transm. 43: 133–143.Google Scholar
  96. Madl, J.E., and Allen, D.L., 1995, Hyperthermia depletes adenosine triphosphate and decreases glutamate uptake in rat hippocampal slices. Neuroscience 69: 395–405.PubMedCrossRefGoogle Scholar
  97. Marek, G., Vosmer, G., and Seiden, L.S., 1990, Dopamine uptake inhibitors block long-term neurotoxic effects of methamphetamine upon dopaminergic neurons. Brain Res. 513: 274–279.PubMedCrossRefGoogle Scholar
  98. Martin, F.R., Sanchez-Ramos, J., and Rosenthal, M., 1991, Selective and non-selective effects of MPTP on oxygen consumption in rat striatal and hippocampal slices. J. Neurochem. 57 1340–1346.PubMedCrossRefGoogle Scholar
  99. Matarredona, E.R., Santiago, M., Machado, A., and Cano, J., 1997, Lack of involvement of glutamate-induced excitotoxicity in MPP+ toxicity in striatal dopamine terminals: possible involvement of ascorbate. Br. J. Pharmacol. 121: 1038–1044.PubMedCrossRefGoogle Scholar
  100. Matsubara, K., Idzu, T., Kobayashi, Y., Gonda, T., OkunishiH. and Kimura, K., 1996, Differences in dopamine efflux induced by MPP+ and (3-carbolinium in the striatum of conscious rats. Eur. J. Pharmacol. 315: 145–151.PubMedCrossRefGoogle Scholar
  101. Matsuda, L.A., Schmidt, C.J., Gibb, J.W., and Hanson, G.R., 1987, Ascorbic acid-deficient condition alters central effects of methamphetamine. Brain Res. 400: 176–180.PubMedCrossRefGoogle Scholar
  102. Matthews, R.J., Beal, M.F., Fallon, J., Fedorchak, K., Huang, P.L., Fishman, M.C., and Hyman, B.T., 1997, MPP+-induced substantia nigra degeneration is attenuated in nNOS knockout mice. Neurobiol. Dis. 4: 114–121.PubMedCrossRefGoogle Scholar
  103. McNaught, K.S., and Jenner, P., 1999, Altered glial function causes neuronal death and increased neuronal susceptibility to 1-methyl-4-phenylpyridinium-and 6-hydroxydopamine-induced toxicity in astrocytic/ventral mesencephalic co-cultures. J. Neurochem. 73: 2469–2476.PubMedCrossRefGoogle Scholar
  104. Meiergerd, S.M., Patterson, T.A., and Schenk, J.O., 1993, D2 receptors may modulate the function of the striatal transporter for dopamine: kinetic evidence from studies in vitro and in vivo. J. Neurochem. 61: 764–767.PubMedCrossRefGoogle Scholar
  105. Merino, M., Vizuete, M.L., Cano, L., and Machado, A., 1999, The non-NMDA glutamate receptor antagonists 5-cyano-7-nitroquinoxaline-2,3-dione and 2,3-dihydroxy-6-nitrosulfamoylbenzo(f)quinoxaline, but not NMDA antagonists, block the intrastriatal neurotoxic effect of MPP+. J. Neurochem. 73: 750–757.PubMedCrossRefGoogle Scholar
  106. Mithöfer, K., Sandy, M.S., Smith, M.T., and Di Monte, D., 1992, Mitochondrial poisons cause depletion of reduced glutathione in isolated hepatocytes. Arch. Biochem. Biophys. 295: 132–136.PubMedCrossRefGoogle Scholar
  107. Mizuno, Y., Saitoh, T., and Sone, N., 1987, Inhibition of mitochondrial a-ketoglutarate dehydrogenase by 1methyl-4-phenylpyridinium ion. Biochem. Biophys. Res. Commun. 143: 971–976.PubMedCrossRefGoogle Scholar
  108. Mizuno, Y., Matuda, S., Yoshino, H., MoriH. Hattori, N., and Ikebe, S.-J., 1994, An immunohistochemical study on a-ketoglutarate dehydrogenase complex in Parkinson’s disease. Ann. Neurol. 35: 204–210.PubMedCrossRefGoogle Scholar
  109. Moszczynska, A., Turenne, S., and Kish, S.J., 1998, Rat striatal levels of the antioxidant glutathione are decreased following binge administration of methamphetamine. Neurosci. Lett. 355: 49–52.CrossRefGoogle Scholar
  110. Nash, J.F., and Yamamoto, B.K., 1992, Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4-methylenedioxymethamphetamine. Brain Res. 581: 237–243.PubMedCrossRefGoogle Scholar
  111. Novelli, A., Reilly, J.A., Lysko, P.G., and Henneberry, R.C., 1988, Glutamate becomes neurotoxic when intracellular energy levels are reduced. Brain Res. 451: 205–212.PubMedCrossRefGoogle Scholar
  112. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A., and Prochiantz, A., 1984, Magnesium gates glutamate-activated channels in mouse central neurons. Nature 307: 462–465.PubMedCrossRefGoogle Scholar
  113. O’Dell, S.J., Weihmuller, F.B., and Marshall, J.F., 1991, Multiple methamphetamine injections induce marked increases in extracellular dopamine which correlate with subsequent neurotoxicity. Brain Res. 564: 256–260.PubMedCrossRefGoogle Scholar
  114. Oishi, T., Hasegawa, E., and Murai, Y., 1993, Sulfhydryl drugs reduce neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse. J. Neural Transm. (P-D Dement. Sect.] 6: 45–52.CrossRefGoogle Scholar
  115. Olney, J.W., Zorumski, C., Price, M.T., and Labruyere, J., 1990, L-Cysteine, a bicarbonate-sensitive excitotoxin. Science 248: 596–599.PubMedCrossRefGoogle Scholar
  116. Olsen, R.J. and Justice, J.B., 1993, Quantitative microdialysis under transient conditions. Anal. Chem. 65: 1017–1022.CrossRefGoogle Scholar
  117. Palmer, C., Roberts, R.L., and Bero, C., 1994, Deferoxamine posttreatment reduces brain injury in neonatal rats. Stroke 25: 1039–1045.PubMedCrossRefGoogle Scholar
  118. Patt, A., Horesh, I.R., Berger, E.M., Harken, A.H., and Repine, J.E., 1990, Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. J. Pediatr. Surg. 25: 224–228.PubMedCrossRefGoogle Scholar
  119. Prince, J.A., Yassin, M.S., and Oreland, L., 1998, Normalization of cytochrome c oxidase activity in the rat brain by neuroleptics after chronic treatment with PCP or methamphetamine. Neuropharmacology 36: 1665–1678.CrossRefGoogle Scholar
  120. Przedborski, S., Kostic, V., Jackson-Lewis, V., Naini, A.B., Simonettá, S., Fah, 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.PubMedGoogle Scholar
  121. Pu, C., Broening, H.W., and Vorhees, C.V., 1996, Effect of methamphetamine on glutamate-positive neurons in the adult and developing rat somatosensory cortex. Synapse 23: 328–334.PubMedCrossRefGoogle Scholar
  122. Puka-Sundvall, M., Sandberg, M., and Hagberg, H. 1997, Brain injury after hypoxia-ischemia in newborn rats: relationship to extracellular levels of excitatory amino acids and cysteine. Brain Res. 750: 325–328.PubMedCrossRefGoogle Scholar
  123. Pullan, L.M., Olney, J.W., Price, M.T., Compton, R.P., Hood, W.F., Michel, J., and Monahan, J.B., 1987, Excitatory amino acid receptor potency and subclass specificity of sulfur-containing amino acids. J. Neurochem. 49: 1301–1307.PubMedCrossRefGoogle Scholar
  124. Pulsinelli, W.A., and Duffy, T.E., 1983, Regional energy balance in the rat brain after transient forebrain ischemia. J. Neurochem. 40: 1500–1503.PubMedCrossRefGoogle Scholar
  125. Quijano, C., Alvarez, B., Gatti, R.M., Augusto, O., and Radi, R., 1997, Pathways of peroxynitrite oxidation of thiol groups. Biochem. J. 322 (Part 1): 167–173.PubMedGoogle Scholar
  126. Raiteri, M., Cerrito, F., Cervoni, A.M., and Levi, G., 1979, Dopamine can be released by two mechanisms differentially affected by the dopamine transporter inhibitor nomifensine. J. Pharmacol. Exp. Therap. 208: 195–202.Google Scholar
  127. Ramsay, R.R., Dadgar, J., Trevor, A., and Singer, T.P., 1986, Energy-driven uptake of N-methyl-4- phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP. Life Sci. 39: 581–588.PubMedCrossRefGoogle Scholar
  128. Ransom, B.R., Kunis, D.M., Irwin, I., and Langston, J.W., 1987, Astrocytes convert the parkinsonian inducing neurotoxin, MPTP, to its active metabolite, MPP+. Neurosci. Lett. 75: 323–328.PubMedCrossRefGoogle Scholar
  129. Raps, S.P., Lai, J.C.K., Hertz, L., and Cooper, A.J.L., 1989, Glutathione is present in high concentrations in cultured astrocytes but not cultured neurons. Brain Res. 493: 398–401.PubMedCrossRefGoogle Scholar
  130. Reed, D.J., and Savage, M.K., 1995, Influence of metabolic inhibitors on mitochondrial permeability transition and glutathione status. Biochim. Biophys. Acta 1271: 43–45.PubMedCrossRefGoogle Scholar
  131. Rehncrona, S., Folbergrovã, J., Smith, D.S., and Siesjö, B. 1980, Pronounced incomplete cerebral ischemia and subsequent recirculation on cortical concentrations of oxidized and reduced glutathione in the rat. J. Neurochem. 34: 477–486.PubMedCrossRefGoogle Scholar
  132. Revuelta, M., Romero-Ramos, M., Venero, J.L., Milian, F., Machado, A., and Cano, J., 1997, Less-induced MPP+ neurotoxicity on striatal slices from guinea pigs fed with a vitamin C lacking diet. Neuroscience 77: 167–174.PubMedCrossRefGoogle Scholar
  133. Ricaurte, G.A., Schuster, C.R., and Seiden, L.S., 1980, Long-term effects of repeated methamphetamine administration on dopaminergic and serotonergic neurons in the rat brain: a regional study. Brain Res. 193: 153–160.PubMedCrossRefGoogle Scholar
  134. Ricaurte, G.A., Fuller, R.W., Perry, K.W., Seiden, L.S., and Schuster, C.R., 1983, Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphetamine and d-amphetamine. Neuropharmacology 22: 1165–1169.PubMedCrossRefGoogle Scholar
  135. Rollema, H. Damsma, G., Horn, A.S., De Vries, J.B. and Westerink, B.H.C., 1986, Brain dialysis in conscious rats reveals an instantaneous massive release of striatal dopamine in response to MPP+. Eur. J. Pharmacol. 126: 345–346.PubMedCrossRefGoogle Scholar
  136. Rose, S., Hindmarsh, J.G., and Jenner, P., 1999, Neuronal nitric oxide synthase inhibition reduces MPP+evoked hydroxyl radical formation but not dopamine efflux in rat striatum. J. Neural Transm. 106 477–486.PubMedCrossRefGoogle Scholar
  137. Rowe, D.B., Le, W., Smith, R.G., and Appel, S.H., 1998, Antibodies from patients with Parkinson’s disease react with protein modified by dopamine oxidation. J. Neurosci. Res. 53: 551–558.PubMedCrossRefGoogle Scholar
  138. Royland, J.E., and Langston, J.W., 1998, MPTP: A dopaminergic neurotoxin, in Highly Selective Neurotoxins: Basic and Clinical Applications (R.M. Kostrzewa, Ed.), Humana Press, Totowa, N.J., pp. 141–194.Google Scholar
  139. Sagara, J., Miura, K., and Bannai, S., 1993a, Cystine uptake and glutathione level in fetal brain cells in primary culture and suspension. J. Neurochem. 61: 1667–1671.CrossRefGoogle Scholar
  140. Sagara, J., Miura, K., and Bannai, S., 1993b, Maintenance of neuronal glutathione by glial cells. J. Neurochem. 61: 1672–1676.CrossRefGoogle Scholar
  141. Saggu, H., Cooksey, J., Dexter, D., Wells, F.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.PubMedCrossRefGoogle Scholar
  142. Santiago, M., Matarredona, E.R., Granero, L., Cano, J., and Machado, A., 1997, Neuroprotective effects of the iron chelator desferrioxamine against MPP+ toxicity on striatal dopaminergic terminals. J. Neurochem. 68: 732–738.PubMedCrossRefGoogle Scholar
  143. Schapira, A.H.V., Mann, V.M., Cooper, J.N., Dexter, D., Daniel, S.E., Jenner, P., Clark, J.B., and Marsden, C.D., 1990, Anatomic and disease specificity of NADH-CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J. Neurochem. 55: 2142–2145.PubMedCrossRefGoogle Scholar
  144. Schulz, J.B. Matthews, R.T., and Beal, M.F., 1995, Role of nitric oxide in neurodegenerative diseases. Curr. Opin. Neurol. 8: 480–486.PubMedCrossRefGoogle Scholar
  145. Schulz, J.B., Matthews, R.T., Klockgether, T., Dichgans, J. and Beal, M.F., 1997, The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases. Mol. Cell. Biochem. 174: 193–197.PubMedCrossRefGoogle Scholar
  146. Seelig, G.F., and Meister, A., 1985, Glutathione biosynthesis; y-glutamylcysteine synthetase from rat kidney. Meth. Enzymol. 113: 379–390.PubMedCrossRefGoogle Scholar
  147. Sensi, S.L., Yin, H.Z., Carriedo, S.G., Rao, S.S., and Weiss, J.H., 1999, Preferential Zn2+ influx through Ca2+ permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production. Proc. Nat. Acad. Sci. U.S.A. 96: 2414–2419.CrossRefGoogle Scholar
  148. Shen, X.-M., and Dryhurst, G., 1996a, Further insights into the influence of L-cysteine on the oxidation chemistry of dopamine: reaction pathways of potential relevance to Parkinson’s disease. Chem. Res. Toxicol. 9: 751–763.CrossRefGoogle Scholar
  149. Shen, X.-M., and Dryhurst, G., 1996b, Oxidation chemistry of (-)-norepinephrine in the presence of Lcysteine. J. Med. Chem. 39 2018–2029.CrossRefGoogle Scholar
  150. Shen, X.-M., Li, H., and Dryhurst, G., 2000, Oxidative metabolites of 5-S-cysteinyldopamine inhibit the aketoglutarate dehydrogenase complex: possible relevance to the pathogenesis of Parkinson’s disease. J. Neural Transm. 00: 00–00.Google Scholar
  151. Sian, J.,Dexter, D., Lees, A., Daniel, S., Agid, Y., Javoy-Agid, F., Jenner, P., and Marsden, C.D., 1994a, Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting the basal ganglia. Ann. Neurol. 36: 348–355.PubMedCrossRefGoogle Scholar
  152. Sian, J., Dexter, D.T., Lees, A.J., Daniel, S., Jenner, P., and Marsden, C.D., 1994b, Glutathione-related enzymes in the brain in Parkinson’s disease. Ann. Neural. 36: 356–361.CrossRefGoogle Scholar
  153. Sims, N.R., 1991, Selective impairment of respiration in mitochondria isolated from brain subregions following transient forebrain ischemia in the rat. J. Neurochem. 56: 1836–1844.PubMedCrossRefGoogle Scholar
  154. Sims, N.R., and Zaidan, E., 1995, Biochemical changes associated with selective neuronal death following short-term cerbral ischaemia. Int. J. Biochem. Cell Biol. 27: 531–550.PubMedCrossRefGoogle Scholar
  155. Slivka, A., and Cohen, G., 1993, Brain ischemia markedly elevates levels of the neurotoxic amino acid, cysteine. Brain Res. 608: 33–37.PubMedCrossRefGoogle Scholar
  156. Smith, T.S., and Bennett, J.P., 1997, Mitochondrial toxins in models of neurodegenerative disease.I. In vivo brain hydroxyl radical production during systemic MPTP treatment or following microdialysis infusion of methylpyridinium or azide ions. Brain Res. 765: 183–188.PubMedCrossRefGoogle Scholar
  157. Smith, T.S., Swerdlow, R.H., Parker, W.D., and BennettJ.P. 1994, Reduction of MPP+-induced hydroxyl radical formation and nigrostriatal MPTP toxicity by inhibiting nitric oxide synthase. Neuroreport 5: 2598–2600.PubMedCrossRefGoogle Scholar
  158. Sonsalla, P.K., Gibb, J.W., and Hanson, G.R., 1986, Roles of D1 and D2 dopamine receptor subtypes in mediating the methamphetamine-induced changes in monoamine systems. J. Pharmacol. Exp. Therap. 238: 932–937.Google Scholar
  159. Sonsalla, P.K., Nicklas, W.J., and Heikkila, R.E., 1989, Roles for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic neurotoxicity. Science 243: 398–400.PubMedCrossRefGoogle Scholar
  160. Sonsalla, P.K., Jochnowitz, N.D., Zeevalk, G.D., Oostveen, J.A., and Hall, E.D., 1996, Treatment of mice with methamphetamine produces cell loss in the substantia nigra. Brain Res. 738 172–175.PubMedCrossRefGoogle Scholar
  161. Spencer, J.P.E. Jenner, P., Daniel, S.E., Lees, A.J., Marsden, C.D., and Halliwell, B., 1998, Conjugates of catecholamines with cysteine and GSH in Parkinson’s disease. Possible mechanisms of formation involving reactive oxygen species. J. Neurochem. 71: 2112–2122.PubMedCrossRefGoogle Scholar
  162. Sriram, K., Pai, K.S., Boyd, M.R., and Ravindranath, V., 1997, Evidence for generation of oxidative stress in brain by MPTP: in vitro and in vivo studies in mice. Brain Res. 749: 44–52.PubMedCrossRefGoogle Scholar
  163. Ste-Marie, L., Vachon, P., Vachon, L., Bemeur, C., Guertin, M.C., and Montgomery, J., 2000, Hydroxyl radical production in the cortex and striatum in a rat model of focal cerebral ischemia. Can. J. Neurol. 27 152–159.Google Scholar
  164. Stephens, S.E., and Yamamoto, B.K., 1994, Methamphetamine-induced neurotoxicity: roles for glutamate and dopamine efflux. Synapse 17: 203–209.CrossRefGoogle Scholar
  165. Steranka, L.R., and Rhina, A.W., 1987, Effect of cysteine on the persistent depletion of brain monoamines by amphetamine, p-chloroamphetamine and MPTP. Eur. J. Pharmacol. 133: 191–197.PubMedCrossRefGoogle Scholar
  166. Stole, E., Smith, T.K., Manning, J.M., and Meister, A., 1994, Interaction of γ-glutamyl transpeptidase with acivicin. J. Biol. Chem. 269: 21435–21439.PubMedGoogle Scholar
  167. Stone, D.M., Johnson, M., Hanson, G.R., and Gibb, J.W., 1999, Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves oxidation of sulfhydryl sites. Eur. J. Pharmacol. 172: 93–97.Google Scholar
  168. Srivastava, R., Brouillet, E., Beal, M.F., Storey, E., and Hyman, B.T., 1993, Blockade of 1-methyl-4phenylpyridinium (MPP+) nigral toxicity in the rat by prior decortication or MK-801 treatment: a stereological estimate of neuronal loss. Neurobiol. Aging 14: 295–301.PubMedCrossRefGoogle Scholar
  169. Storey, E., Hyman, B.T., Jenkins, B., Brouillet, E., Miller, J.M., Rosen, B.R. and Beal, M.F., 1992, 1Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. J. Neurochem. 58: 1975–1978.PubMedCrossRefGoogle Scholar
  170. Swerdlow, R.H., Parks, J.H., Miller, S.W., Tuttle, J.B., Trimmer, P.A., Sheehan, J.P., Bennett, J.P., Davis, R.E., and Parker, W.D., 1996, Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann. Neurol. 40: 663–671.PubMedCrossRefGoogle Scholar
  171. Tate, S.S., and Meister, A., 1985, y-Gluthmyl transpeptidase from kidney. Meth. Enzymol. 113: 400–437.PubMedCrossRefGoogle Scholar
  172. Thomas, B., Muralikrishnan, D., and Mohanakumar, K.P., 2000, In vivo hydroxyl radical generation in the striatum following systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Brain Res. 852: 221–224.PubMedCrossRefGoogle Scholar
  173. Volicer, L., Langlais, P.J., Matson, W.R., Mark, K.A., and Gamache, P.H. 1985, Serotoninergic system in dementia of the Alzheimer type: abnormal forms of 5-hydroxytryptophan and serotonin in cerebrospinal fluid. Arch. Neurol. 42: 1158–1161.PubMedCrossRefGoogle Scholar
  174. Wagner, K.R., Kleinholz, M., and Myers, R.E., 1990, Delayed onset of neurologic deterioration following anoxia/ischemia coincides with appearance of impaired brain mitochondrial respiration and decreased cytochrome oxidase activity. J. Cereb. Blood Flow Metab. 10: 417–423.PubMedCrossRefGoogle Scholar
  175. Wang, X.F., and Cynader, M.X., 2000, Astrocytes provide cysteine to neurons by releasing glutathione. J. Neurochem. 74: 1434–1442.PubMedCrossRefGoogle Scholar
  176. Wefers, H., and Sies, H., 1983, Oxidation of glutathione by the superoxide radical to the disulfide and sulfonate yielding singlet oxygen. Eur. J. Biochem. 137: 29–36.PubMedCrossRefGoogle Scholar
  177. Weinberger, J., Cohen, G., and Nieves-Rosa, J., 1983, Nerve terminal damage in cerebral ischemia: greater susceptibility of catecholamine nerve terminals relative to serotonergic nerve terminals. Stroke 14: 986–989.PubMedCrossRefGoogle Scholar
  178. Weiner, H.L., Hashim, A., Lajtha, A., and Sershen, H., 1988, (-)-2-Oxo-4-thiazolidine carboxylic acid attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced neurotoxicity. Res. Commun. Subst. Abuse 9: 53–68.Google Scholar
  179. Wong, K.-S., Goyal, R.N., Wrona, M.Z., Blank, C.L., and Dryhurst, G., 1993, 7-S-Glutathiony1tryptamine-4,5-dione: a possible aberrant metabolite of serotonin. Biochem. Pharmacol. 46: 1637–1652.PubMedCrossRefGoogle Scholar
  180. Wood, N., 1997, Genes and parkinsonism. J. Neurol. Neurosurg. Psychiatry 62: 305–309.PubMedCrossRefGoogle Scholar
  181. Wrona, M.Z., and Dryhurst, G., 1998, Oxidation of serotonin by superoxide radical: implications to neurodegenerative brain disorders. Chem. Res. Toxicol. 11: 639–650.PubMedCrossRefGoogle Scholar
  182. Wu, E.Y., Smith, M.T., Bellomo, G., and Di Monte, D., 1990, Relationship between mitochondrial transmembrane potential, ATP concentration, and cytotoxicity in isolated rat hepatocytes. Arch. Biochem. Biophys. 282 358–362.PubMedCrossRefGoogle Scholar
  183. Wullner, U., Loschmann, P.A., Schulz, J.B., Schmid, A., Dringen, R., Eblen, F., Turski, L., and Klockgether, T., 1996, Glutathione depletion potentiates MPTP and MPP+ toxicity in nigral dopaminergic neurones. Neuroreport 7: 921–923.PubMedCrossRefGoogle Scholar
  184. Xie, C.X., St. Pyrek, J., Porter, W.H., and Yokel, R.A., 1995, Hydroxyl radical generation in rat brain is initiated by iron not aluminum, as determined by microdialysis with salicylate trapping and GS-MS analysis. Neurotoxicology 16: 489–496.PubMedGoogle Scholar
  185. Xin, W., Shen, X.-M., Li, H., and Dryhurst, G., 2000, Oxidative metabolites of 5-S-cysteinylnorepinephrine are irreversible inhibitors of mitochondrial complex I and the a-ketoglutarate dehydrogenase and pyruvate dehydrogenase complexes: possible implications for neurodegenerative brain disorders. Chem. Res. Toxicol. 00 00–00.Google Scholar
  186. Xu, Y.M., Stokes, A.H., Roskoski, R., and Vrana, K.E., 1998, Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. J. Neurosci. 54: 691–697.CrossRefGoogle Scholar
  187. Yamamoto, M., Sakamoto, N., Iwai, A., Yatsugi, S., Hidaka, K., Noguchi, K., and Yuasa, T., 1993, Protective actions of YM737, a new glutathione analog, against cerebral ischemia in rats. Res. Commun. Chem. Pathol. Pharmacol. 81: 221–232.PubMedGoogle Scholar
  188. Yamamoto, B., and Zhu, W., 1998, The effects of methamphetamine on the production of free radicals and oxidative stress. J. Pharmacol. Exp. Therap. 287: 107–114.Google Scholar
  189. Yang, G., Chan, P.H., Chen, J., Carlson, E., Chen, S.F., Weinstein, P., Epstein, C.J., and Kamii, H. 1994, Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke 25: 165–170.PubMedCrossRefGoogle Scholar
  190. Yang, C.S., Lin, N.N., Liu, L., Tsai, P.J., and Kuo, J.S., 1995, Lowered brain glutathione by diethylmaleate decreased the glutamate release by cerebral ischemia in the anesthetized rat. Brain Res. 698, 237–240.PubMedCrossRefGoogle Scholar
  191. Yang, C.S., Lin, N.N., Tsai, P.J., Liu, L., and Kuo, J.S., 1996, In vivo evidence of hydroxyl radical formation induced by elevation of extracellular glutamate after cerebral ischemia in the cortex of anesthetized rats. Free Rad. Biol. Med. 20 245–250.PubMedCrossRefGoogle Scholar
  192. Yang, H., Peters, J.L., Allen, C., Chern, S.-S., Coalson, R.D., and Michael, A.C., 2000, A theoretical description of microdialysis with mass transport coupled to chemical events. Anal. Chem. 72: 2042–2049.PubMedCrossRefGoogle Scholar
  193. Yong, V.W., Perry, T.L., and Krisman, A.A., 1986, Depletion of glutathione in brainstem of mice caused by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is prevented by antioxidant pretreatment. Neurosci. Lett. 63: 56–60.PubMedCrossRefGoogle Scholar
  194. Yoshida, T., Tanaka, M., Somomatsu, A., and Hirai, S., 1995, Activated microglia cause superoxide-mediated release of iron from ferritin. Neurosci. Lett. 190: 21–24.PubMedCrossRefGoogle Scholar
  195. Zaidan, E., Sheu, K.F., and Sims, N.R., 1998, The pyruvate dehydrogenase complex is partially inactivated during early recirculation following short-term forebrain ischemia in rats. J. Neurochem. 70: 233–241.PubMedCrossRefGoogle Scholar
  196. Zängerle, L., Cuenod, M., Winterhalter, K.H., and Do, K.Q., 1992, Screening of thiol compounds: depolarization-induced release of glutathione and cysteine from rat brain slices. J. Neurochem. 59: 181–189.PubMedCrossRefGoogle Scholar
  197. Zeevalk, G.D., and Nicklas, W.J., 1991, Mechanisms underlying initiation of excitotoxicity associated with metabolic inhibition. J. Pharmacol. Exp. Therap. 257: 870–878.Google Scholar
  198. Zeevalk, G.D., Davis, N., Hyndman, A.G., and Nicklase, W.J., 1998, Origins of the extracellular glutamate released during total metabolic blockade of the immature retina. J. Neurochem. 71:2373–2381.PubMedCrossRefGoogle Scholar
  199. Zeevalk, G.D., Manzino, L., and Sonsalla, P.K., 2000, NMDA receptors modulate dopamine loss due to energy impairment in the substantia nigra but not striatum. Exp. Neurol. 161: 638–646.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Glenn Dryhurst
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of OklahomaNormanUSA

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