The intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp): A new rodent model to test palliative and neuroprotective agents for parkinson's disease

Current Pharmaceutical Design

Volumn 17, Issue 5, 2011, Pages 489-507

  Prediger, Rui D S ^a   Aguiar Jr , Aderbal S ^a   Moreira, Eduardo L G ^a   Matheus, Filipe C ^a   Castro, Adalberto A ^a   Walz, Roger ^a   de Bem, Andreza F ^a   Latini, Alexandra ^a   Tasca, Carla I ^a   Farina, Marcelo ^a   Raisman Vozari, Rita ^b  

^a FEDERAL UNIVERSITY OF SANTA CATARINA   (Brazil)

^b SORBONNE UNIVERSITÉ   (France)

Author keywords

Animal model; Antiparkinsonian drugs screening; Behavior; Intranasal mptp; Motor symptoms; Non motor symptoms; Parkinson's disease; Pathogenic mechanisms

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; ANTIPARKINSON AGENT; TYROSINE 3 MONOOXYGENASE;

APOPTOSIS; ARTICLE; BEHAVIOR DISORDER; BRAIN REGION; CENTRAL NERVOUS SYSTEM; DOPAMINERGIC NERVE CELL; DYSKINESIA; EXCITOTOXICITY; HUMAN; MOTOR DYSFUNCTION; NEUROPROTECTION; NONHUMAN; OLFACTORY BULB; OXIDATIVE STRESS; PALLIATIVE THERAPY; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PSYCHOSIS; SUBSTANTIA NIGRA PARS COMPACTA;

1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; ADMINISTRATION, INTRANASAL; ANIMALS; BEHAVIOR, ANIMAL; BIOGENIC MONOAMINES; BRAIN; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; HUMANS; MPTP POISONING; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE;

EID: 79953318386     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161211795164095     Document Type: Article

References (212)

1. Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychia-try Clin Neurosci 2002; 14: 223-36.
2. Mayeux R. Epidemiology of neurodegeneration. Annu Rev Neuro-sci 2003; 26: 81-104.
3. O'Brien JA, Ward A, Michels SL, Tzivelekis S, Brandt NJ. Economic burden associated with Parkinson disease. Drug Benefit Trends 2003; 21: 179-90.
4. Hirsch E, Graybiel AM, Agid YA. Melanized dopamine neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 1988; 334: 345-8.
5. Allain H, Bentué-Ferrer D, Akwa Y. Disease-modifying drugs and Parkinson's disease. Prog Neurobiol 2008; 84: 25-39.
6. Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskine-sias and motor fluctuations as estimated from the cumulative litera-ture. Mov Disord 2001; 16: 448-58.
7. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res 2004; 318: 121-34.
8. Chaudhuri KR, Healy DG, Schapira AH; National Institute for Clinical Excellence. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 2006; 5: 235-45.
9. Schapira AH, Bezard E, Brotchie J, et al. Novel pharmacological targets for the treatment of Parkinson's disease. Nat Rev Drug Discov 2006; 5: 845-54.
10. Obeso JA, Rodriguez-Oroz MC, Goetz CG,. Missing pieces in the Parkinson's disease puzzle. Nat Med 2010; 16(6): 653-61.
11. Schapira AH. Disease modification in Parkinson's disease. Lancet Neurol 2004; 3: 362-8.
12. Dawson TM, Dawson VL. Neuroprotective and neurorestorative strategies for Parkinson's disease. Nat Neurosci 2002; 5: 1058-61.
13. Schapira AH, Olanow CW. Neuroprotection in Parkinson's dis-ease: mysteries, myths and misconceptions. JAMA 2004; 291: 358-64.
14. Meissner W, Hill MO, Tison F, Gross CE, Bezard E. Neuroprotec-tive strategies for Parkinson's disease: conceptual limits of animal models and clinical trials. Trends Pharmacol Sci 2004; 25: 249-53.
15. Riederer P, Wuketich S. Time course of nigrostriatal degeneration in Parkinson's disease. A detailed study of influential factors in human brain amine analysis. J Neural Transm 1976; 38: 277-301.
16. Gerlach M, Foley P, Riederer P. The relevance of preclinical studies for the treatment of Parkinson's disease. J Neurol 2003; 250: 31-4.
17. Gerlach M, Riederer P. Animal models of Parkinson's disease: an empirical comparison with the phenomenology of the disease in man. J Neural Transm 1996; 103: 987-1041.
18. Beal MF. Experimental models of Parkinson's disease. Nat Rev Neurosci 2001; 2: 325-34.
19. Prediger RD, Batista LC, Medeiros R, Pandolfo P, Florio JC, Takahashi RN. The risk is in the air: intranasal administration of MPTP to rats reproducing clinical features of Parkinson's disease. Exp Neurol 2006; 202: 391-403.
20. Franco J, Prediger RD, Pandolfo P, Takahashi RN, Farina M, Dafre AL. Antioxidant responses and lipid peroxidation following intra-nasal1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ad-ministration in rats: increased susceptibility of olfactory bulb. Life Sci 2007; 80: 1906-14.
21. Prediger RD, Rial D, Medeiros R, Figueiredo CP, Doty RL, Taka-hashi RN. An intranasal MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) rat model of Parkinson's disease. Ann N Y Acad Sci 2009; 1170: 629-36.
22. Prediger RD, Aguiar AS Jr, Rojas-Mayorquin AE, et al. Single intranasaladministrationof1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in C57BL/6 mice models early preclinical phase of Parkinson's disease. Neurotoxic Res 2010; 17: 115-29.
23. Moreira EL, Rial D, Aguiar Jr. AS, et al. Proanthocyanidin-rich fraction from Croton celtidifolius Baill confers neuroprotection in theintranasal1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rat model of Parkinson's disease. J Neural Transm 2010; 117(12): 1337-51.
24. Vila M, Przedborski S. Targeting programmed cell death in neu-rodegenerative diseases. Nat Rev Neurosci 2003; 4(5): 365-75.
25. +)-analogs on the respiratory chain of bo-vine heart mitochondria. Arch Biochem Biophys 1997; 337: 69-74.
26. Gainetdinov RR, Fumagalli F, Jones SR, Caron MG. Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter. J Neurochem 1997; 69: 1322-5.
27. Di Monte DA. The environment and Parkinson's disease: is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol 2003; 2(9): 531-8.
28. Ross CA, Smith WW. Gene-environment interactions in Parkin-son's disease. Parkinsonism Relat Disord 2007; 13(Suppl): S309-15.
29. Uversky VN. Neurotoxicant-induced animal models of Parkinson's disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration. Cell Tissue Res 2004; 318(1): 225-41.
30. Doty, R.L. The olfactory vector hypothesis of neurodegenerative disease: is it viable? Ann. Neurol 2008; 63: 7-15.
31. Barnett EM, Perlman S. The olfactory nerve and not the trigeminal nerve is the major site of CNS entry for mouse hepatitis virus, strain JHM. Virology 1993; 194: 185-91.
32. Hastings L, Evans JE. Olfactory primary neurons as a route of entry for toxic agents into the CNS. Neurotoxicology 1991; 12: 707-14.
33. Zatta P, Favarato M, Nicolini M. Deposition of aluminum in brain tissues of rats exposed to inhalation of aluminum acetylacetonate. Neuroreport 1993; 4: 1119-22.
34. Tjälve H, Henriksson J, Tallkvist J, Larsson B S, Lindquist N G. Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol Toxicol 1996; 79: 347-56.
35. Normandin L, Ann Beaupre L, Salahi F, et al. Manganese distribu-tion in the brain and neurobehavioral changes following inhalation exposure of rats to three chemical forms of manganese. Neurotoxi-cology 2004; 25: 433-41.
36. Doty R L, Deems D, Stellar S. Olfactory dysfunction in Parkin-son's disease: A general deficit unrelated to neurologic signs, dis-ease state, or disease duration. Neurology 1988; 38: 1237-44.
37. Hawkes C H, Del Tredici K, Braak H. Parkinson's disease: a dual-hit hypothesis. Neuropathology and Applied Neurobiology 2007; 33: 599-614.
38. Doty RL. Cranial nerve I: olfaction. In: Goltz CG, Pappert EJ, Ed. Textbook of clinical neurology. Philadelphia: WB Saunders Co. 1998; pp. 90-101.
39. Merkus FW, Vn den Berg MP. Can nasal drug delivery bypass the blood-brain barrier?: questioning the direct transport theory. Drugs R D 2007; 8(3): 133-44.
40. Pardridge WM. Drug delivery to the brain. J Cereb Blood Metab 1997; 17 (7): 713-31.
41. Barnett EM, Perlman S. The olfactory nerve and not the trigeminal nerve is the major site of CNS entry for mouse hepatitis virus, strain JHM. Virology 1993; 1: 185-91.
42. Meredith M. Human vomeronasal organ function: a critical review of best and worst cases. Chemical Senses 2001; 26(4): 433-45.
43. Jenner P. Functional models of Parkinson's disease: a valuable tool in the development of novel therapies. Ann Neurol Suppl 2008; 2(Suppl): S16-29.
44. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Sci-ence 1983; 219: 979-80.
45. Bezard E, Dovero S, Prunier C, et al. Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease. J Neurosci 2001; 21: 6853-61.
46. Schmidt N, Ferger B. Neurochemical findings in the MPTP model of Parkinson's disease. J. Neural Transm 2001; 108: 1263-82.
47. Sedelis M, Hofele K, Auburger GW, Morgan S, Huston JP, Schwarting RK. MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain dif-ferences. Behav Genet 2000; 30: 171-82.
48. Przedborski S, Jackson-Lewis V, Naini AB, et al. The parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem 2001; 76: 1265-74.
49. Chiueh C, Markey SP, Burns RS, Johannessen JN, Pert A, Kopin IJ. Neurochemical and behavioral effects of systemic and intrani-graladministrationofN-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the rat. Eur J Pharmacol 1984; 100: 189-94.
50. Kalaria RN, Mitchell MJ, Harik SI. Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine-oxidase activity. Proc Natl Acad Sci USA 1987; 84: 3521-5.
51. Giovanni A, Sieber BA, Heikkila RE, Sonsalla PK. Studies on species sensitivity to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Part 1: Systemic administration. J Pharmacol Exp Ther 1994; 270: 1000-7.
52. Kawano T, Margolis FL. Transsynaptic regulation of olfactory bulb catecholamines in mice and rats. J Neurochem 1982; 39: 342-8.
53. Rojo AI, Montero C, Salazar M, et al. Persistent penetration of MPTP through the nasal route induces Parkinson's disease in mice. Eur J Neurosci 2006; 24: 1874-84.
54. Rojo AI, Cavada C, de Sagarra MR, Cuadrado A. Chronic inhala-tion of rotenone or paraquat does not induce Parkinson's disease mptoms in mice or rats. Exp Neurol 2007; 208(1): 120-6.
55. Doty RL, Bromley SM, Stern MB. Olfactory testing as an aid in the diagnosis of Parkinson's disease: development of optimal discrimi-nation criteria. Neurodegeneration 1995; 4: 93-7.
56. Dubois B, Pillon B. Cognitive deficits in Parkinson's disease. J Neurol 1997; 244: 2-8.
57. Bosboom JL, Stoffers D, Wolters ECH. Cognitive dysfunction and dementia in Parkinson's disease. J Neural Transm 2004; 111: 1303-15.
58. Stebbins GT, Gabrieli JDE, Masciari F, Monti L, Goetz CG. De-layed recognition memory in Parkinson's disease: a role for work-ing memory? Neuropsychologia 1999; 37: 503-10.
59. Lewis SJG, Dove A, Robbins TW, Barker RA, Owen AM. Cogni-tive impairments in early Parkinson's disease are accompanied by reductions in activity in frontostriatal neural circuitry. J Neurosci 2003; 23: 6351-6.
60. Cummings JL, Masterman DL. Depression in patients with Parkin-son's disease. Int J Geriatr Psychiatry 1999; 14: 711-8.
61. Richard IH, Frank S, Mcdermott MP, et al. The ups and downs Parkinson's disease: a prospective study of mood and anxiety fluc-tuations. Cogn Behav Neurol 2004; 17: 201-7.
62. Dluzen DE, Kefalas G. The effects of intranasal infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) upon catecho-lamine concentrations within olfactory bulbs and corpus striatum of male mice. Brain Res 1996; 741: 215-9.
63. Tolosa E, Compta Y, Gaig C. The premotor phase of Parkinson's disease. Parkinsonism Relat Disord 2007; 13: 2-7.
64. Lieberman A. Depression in Parkinson's disease: a review. Acta Neurol Scand 2006; 113: 1-8.
65. Schrag A. Psychiatric aspects of Parkinson's disease: an update. J Neurol 2004; 251: 795-804.
66. Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978; 47: 379-91.
67. Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 1987; 92: 180-5.
68. Petroske E, Meredith GE, Callen S, Totterdell S, Lau YS. Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment. Neuroscience 2001; 106: 589-601.
69. Fornai F, Schlüter OM, Lenzi P, et al. Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc Natl Acad Sci USA 2005; 102: 3413-8.
70. Schintu N, Frau L, Ibba M, Garau A, Carboni E, Carta AR. Pro-gressive Dopaminergic Degeneration in the Chronic MPTP Mouse Model of Parkinson's Disease. Neurotox Res 2009; 16: 127-39.
71. Wright JM, Wall RA, Perry TL, Paty DW. Chronic parkinsonism secondary to intranasal administration of a product of meperidine-analogue synthesis. N Engl J Med 1984; 310-25.
72. Sulzer D. Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease. Trends Neurosci 2007; 30: 244-50.
73. Dawson TM, Dawson VL. Molecular pathways of neurodegenera-tion in Parkinson's disease. Science 2003; 31: 819-22.
74. Nicholls DG, Ferguson SJ. Bioenergetics 3 2002; Academic Press, London.
75. Boveris A, Cadenas E, Stoppani A. Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochem J 1976; 156: 435-44.
76. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 2003; 278: 36027-31.
77. Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 1980; 191: 421-7.
78. Turrens JF. Superoxide production by the mitochondrial respiratory chain. Biosci Rep 1997; 17: 3-8.
79. Bandy B, Davison AJ. Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Radic Biol Med 1990; 8: 523-39.
80. Zhang Y, Marcillat O, Giulivi C, Ernster L, Davies KJ. The oxida-tive inactivation of mitochondrial electron transport chain compo-nents and ATPase. J Biol Chem 1990; 265: 16330-6.
81. Hausladen A, Fridovich I. Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not. J Biol Chem 1994; 269: 29405-8.
82. Chinopoulos C, Adam-Vizi V. Mitochondria deficient in complex I activity are depolarized by hydrogen peroxide in nerve terminals: relevance to Parkinson's disease. J Neurochem 2001; 76: 302-6.
83. Mizuno Y, Ohta S, Tanaka M, et al. Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem Biophys Res Commun 1989; 163: 1450-5.
84. Parker WD, Boyson SJ, Parks JK. Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann Neurol 1989; 26: 719-23.
85. Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. Mitochondrial complex I deficiency in Parkinson's disease. Lancet 1989; 1: 1269.
86. Parker WD, Parks JK, Swerdlow RH. Complex I deficiency in Parkinson's disease frontal cortex. Brain Res 2008; 1189: 215-8.
87. Navarro A, Boveris A, Bandez MJ, et al. Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkin-son disease and in dementia with Lewy bodies. Free Radic Biol Med 2009; 46: 1574-80.
88. Hu MT, Taylor-Robinson SD, Chaudhuri KR, et al. Cortical dys-function in non-demented Parkinson's disease patients: a combined (31)P-MRS and (18)FDG-PET study. Brain 2000; 123: 340-52.
89. Rango M, Bonifati C, Bresolin N. Parkinson's disease and brain mitochondrial dysfunction: a functional phosphorus magnetic reso-nance spectroscopy study. J Cereb Blood Flow Metab 2006; 26: 283-90.
90. Bowen BC, Block RE, Sanchez-Ramos J, et al. Proton MR spec-troscopy of the brain in 14 patients with Parkinson disease. AJNR Am J Neuroradiol 1995; 16: 61-8.
91. Hattingen E, Magerkurth J, Pilatus U, et al. Phosphorus and proton magnetic resonance spectroscopy demonstrates mitochondrial dys-function in early and advanced Parkinson's disease. Brain 2009; 132: 3285-97.
92. Bindoff LA, Birch-Machin M, Cartlidge NE, Parker WD, Turnbull DM. Mitochondrial function in Parkinson's disease. Lancet 1989; 2: 49.
93. Krige D, Carroll MT, Cooper JM, Marsden CD, Schapira AH. Platelet mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson Disease Research Group. Ann Neurol 1992; 32: 782-8.
94. Mann VM, Cooper JM, Krige D, Daniel SE, Schapira AH, Mars-den CD. Brain, skeletal muscle and platelet homogenate mitochon-drial function in Parkinson's disease. Brain 1992; 115: 333-42.
95. Janetzky B, Hauck S, Youdim MB, et al. Unaltered aconitase activity, but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson's disease. Neurosci Lett 1994; 169: 126-8.
96. Mann VM, Cooper JM, Daniel SE, et al. Complex I, iron, and ferritin in Parkinson's disease substantia nigra. Ann Neurol 1994; 36: 876-81.
97. Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, Shults CW. Low platelet mitochondrial complex I and complex II/III ac-tivity in early untreated Parkinson's disease. Ann Neurol 1995; 37: 714-22.
98. Swerdlow RH, Parks JK, Miller SW, et al. Origin and functional consequences of the complex I defect in Parkinson's disease. Ann Neurol 1996; 40: 663-71.
99. Gu M, Cooper JM, Taanman JW, Schapira AH. Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's dis-ease. Ann Neurol 1998; 44: 177-86.
100. Ferrer I. Early involvement of the cerebral cortex in Parkinson's disease: convergence of multiple metabolic defects. Prog Neurobiol 2009; 88: 89-103.
101. Blin O, Desnuelle C, Rascol O, et al. Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy. J Neurol Sci 1994; 125: 95-101.
102. Reichmann H, Janetzky B, Bischof F, et al. Unaltered respiratory chain enzyme activity and mitochondrial DNA in skeletal muscle from patients with idiopathic Parkinson's syndrome. Eur Neurol 1994; 34: 263-7.
103. Mizuno Y, Matuda S, Yoshino H, Mori H, Hattori N, Ikebe S. An immunohistochemical study on alpha-ketoglutarate dehydrogenase complex in Parkinson's disease. Ann Neurol 1994; 35: 204-10.
104. Eve DJ, Nisbet AP, Kingsbury AE, et al. Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson's disease. Brain Res Mol Brain Res 1998; 63: 62-71.
105. Nisoli E, Falcone S, Tonello C, et al. Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc Natl Acad Sci USA 2204; 101: 16507-12.
106. Cameron HA, Kaliszewski CK, Greer CA. Organization of mito-chondria in olfactory bulb granule cell dendritic spines. Synapse 1991; 8: 107-18.
107. Javitch JA, D́AMATO RJ, Strittmatter SM, Snyder SH. Parkin-sonism-inducingneurotoxin,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 1985; 82: 2173-7.
108. Hoppel CI, Grinblatt D, Kwok HC, Aropa PK, Singh MP, Sayre LM. Inhibition of mitochondrial respiration by analogs of 4-phenylpyridine and 1-methyl-4-phenylpyridinium cation (MPP+), the neurotoxic metabolite of MPTP. Biochem Biophys Res Com-mun 1987; 148: 684-93.
109. Davey GP, Tipton KF, Murphy MP. Uptake and accumulation of 1-methyl-4-phenylpyridinium by rat liver mitochondria measured us-ing an ion-selective electrode. Biochem J 1992; 288: 439-43.
110. Ramsay RR, Krueger MJ, Youngster SK, Gluck MR, Casida JE, Singer TP. Interaction of 1-methyl-4-phenylpyridinium ion (MPP+) and its analogs with the rotenone/piericidin binding site of NADH dehydrogenase. J Neurochem 1991;56: 1184-90.
111. Ramsay RR, Steenkamp DJ, Husain M. Reactions of electron-transfer flavoprotein and electron-transfer flavoprotein: ubiquinone oxidoreductase. Biochem J 1987; 241: 883-92.
112. Chan P, Delanney LE, Irwin L, Langston JW, Di Monte D. Rapid ATP loss caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse brain. J Neurochem 1991; 57: 348-51.
113. Henchcliffe C, Beal MF. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 2008; 4(11): 600-9.
114. Nakamura T, Lipton SA. S-Nitrosylation of Critical Protein Thiols Mediates Protein Misfolding and Mitochondrial Dysfunction in Neurodegenerative Diseases. Antioxid Redox Signal 2010(in press). doi:10.1089/ars.2010.3570.
115. Danielson SR, Andersen JK. Oxidative and nitrative protein modi-fications in Parkinson's disease. Free Radic Biol Med 2008; 44(10): 1787-94.
116. Tsang AH, Chung KK. Oxidative and nitrosative stress in Parkin-son's disease. Biochim Biophys Acta 2009; 1792(7): 643-50.
117. Chinta SJ, Andersen JK. Redox imbalance in Parkinson's disease. Biochim Biophys Acta 2008; 1780: 1362-7.
118. Martin HL, Teismann P. Glutathione - a review on its role and significance in Parkinson's disease. Faseb J 2009; 23(10): 3263-72.
119. Hastings TG. The role of dopamine oxidation in mitochondrialdysfunction: implications for Parkinson's disease. J Bioenerg Biomembr 2009; 41(6): 469-72.
120. Dexter DT, Carter CJ, Wells FR, et al. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem 1989; 52: 381-9.
121. Yoritaka AN, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 1996; 93: 2696-2701.
122. Good PF, Hsu A, Werner P, Perl DP, Olanow CW. Protein nitration in Parkinson's disease. J. Neuropathol. Exp Neurol 1998; 57: 338-42.
123. Alam ZI, Jenner A, Daniel SE, et al. Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in8- hydroxyguanine levels in substantia nigra. J Neurochem 1997; 69: 1196-1203.
124. Chun HS, Gibson GE, DeGiorgio LA, Zhang H, Kidd VJ, Son JH. Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism. J Neuro-chem 2001; 76: 1010-21.
125. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003; 39: 889-909.
126. Schober A. Classic toxin-induced animal models of Parkinson's disease: 6-OHDA and MPTP. Cell Tissue Res 2004; 318: 215-24.
127. Miller RL, James-Kracke M, Sun GY, Sun AY. Oxidative and inflammatory pathways in Parkinson's disease. Neurochem Res 2009; 34: 55-65.
128. Przedborski S, Tieu K, Perier C, Vila M. MPTP as a mitochondrial neurotoxic model of Parkinson's disease. J Bioenerg Biomembr 2004; 36: 375-79.
129. Richardson JR, Caudle WM, Guillot TS, et al. Obrigatory role for complex I inhibition in the dopaminergic neurotoxicity of 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Toxicol Sci 2007; 95: 196-204.
130. Hasegawa E, Takeshige K, Oishi T, Murai Y, Minakami S. 1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxi- dation in bovine heart submitochondrial particles. Biochem Bio-phys Res Commun 1990; 170: 1049-55.
131. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implica-tions for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990; 87: 1620-4.
132. Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution and ex-pression. Free Radical Biology & Medicine 2002; 33: 337-49.
133. Przedborski S, Ischiropoulos H. Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson's disease. Antioxidants & Redox Signaling 2005; 7: 685-93.
134. Yong VM, Perry TL, Krisman AA. Depletion of glutathione in brainstem of mice caused by N-methyl-4-ph-enyl-1,2,3,6-tetrahydropyridine is prevented by antioxidant pretreatment. Neu-rosci Lett 1986; 63: 56-60.
135. Hald A, Lotharius J. Oxidative stress and inflammation in Parkin-son's disease: is there a causal link? Exp Neurol 2005; 193: 279-90.
136. Perry TL, Yong VW, Clavier RM, et al. Partial protection from the dopaminergic neurotoxin N-methyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse. Neurosci Lett 1985; 60: 109-14.
137. Wagner GC, Jarvis MF, Carelli RM. Ascorbic acid reduces the dopamine depletion induced by MPTP. Neuropharmacology 1985; 24: 1261-2.
138. Odunze IN, Klaidman LK, Adams JD Jr. MPTP toxicity in the mouse brain and vitamin E. Neurosci Lett 1990; 108: 346-9.
139. Przedborski S, Kostic V, Jackson-Lewis V, et al. Transgenic mice with increased Cu/Zn-superoxide dismutase are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J Neurosci 1992; 12: 1658-67.
140. Klivenyi P, St Clair D, Wermer M, et al. Manganese superoxide dismutase overexpression attenuates MPTP toxicity. Neurobiol Dis 1998; 5: 253-8.
141. Zhang J, Graham DG, Montine TJ, Ho YS. Enhanced N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice deficient in CuZnsuperoxide dismutase or glutathione peroxidase. J Neuropa-thol Exp Neurol 2000; 59: 53-61.
142. Andreassen OA, Ferrante RJ, Dedeoglu A, et al. Mice with a partial deficiency of manganese superoxide dismutase show in-creased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp Neurol 2001; 167: 189-95.
143. Chamorro G, Pérez-Albiter M, Serrano-García N, Mares-Sámano JJ, Rojas P. Spirulina maxima pretreatment partially protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxic-ity. Nutr Neurosci 2006; 9: 207-12.
144. Gupta A, Dhir A, Kumar A, Kulkarni SK. Protective effect of cyclooxygenase (COX)-inhibitors against drug-induced catatonia and MPTP-induced striatal lesions in rats. Pharmacol Biochem Be-hav 2009; 94(2): 219-26.
145. Dringen R, Gutterer JM, Hirrlinger J. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 2000; 267(16): 4912-6.
146. Franco AA, Odom RS, Rando TA. Regulation of antioxidant enzyme gene expression in response to oxidative stress and during differentiation of mouse skeletal muscle. Free Radic Biol Med 1999; 27: 1122-32.
147. Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 2000; 1:120-129.
148. Anglade P, Vyas S, Javoy-Agid F, et al. Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol Histo-pathol 1997; 12: 25-31.
149. Singh S, Dikshit M. Apoptotic neuronal death in Parkinson's dis-ease: involvement of nitric oxide. Brain Res Rev 2007; 54: 233-50.
150. Olanow CW. The pathogenesis of cell death in Parkinson's disease. Mov Disord 2007; 22 Suppl 17: S335-42.
151. Hartley A, Stone JM, Heron C, Cooper JM, Schapira AH. Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: rele-vance to Parkinson's disease. J Neurochem 1994;63:1987-90.
152. Mochizuki H, Nakamura N, Nishi K, Mizuno Y. Apoptosis is induced by 1-methyl-4-phenylpyridinium ion (MPP+) in ventral mesencephalic-striatal co-culture in rat. Neurosci Lett 1994; 170: 191-4.
153. Levy OA, Malagelada C, Greene LA. Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps. Apoptosis 2009; 14: 478-500.
154. Przedborski S, Vila M. The1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model: a tool to explore the pathogenesis of Parkinson's disease. Ann N Y Acad Sci 2003; 991:189-98.
155. Hassouna I, Wickert H, Zimmermann M, Gillardon F. Increase in bax expression in substantia nigra following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment of mice. Neurosci Lett 1996; 204: 85-8.
156. Vila M, Jackson-Lewis V, Vukosavic S, et al. Bax ablation pre-vents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Proc Natl Acad Sci USA 2001; 98: 2837-42.
157. Ouyang M, Shen X. Critical role of ASK1 in the 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells. J Neurochem 2006; 97: 234-44.
158. Karunakaran S, Diwakar L, Saeed U, et al. Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by alpha-lipoic acid. FASEB J 2007; 21:2226-36.
159. Wang W, Shi L, Xie Y,. SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease. Neurosci Res 2004; 48(2): 195-202.
160. Saha AR, Ninkina NN, Hanger DP, Anderton BH, Davies AM, Buchman VL. Induction of neuronal death by alpha-synuclein. Eur J Neurosci 2000; 12: 3073-7.
161. Tanaka Y, Engelender S, Igarashi S, et al. Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Hum Mol Genet 2001; 10:919-26.
162. Dauer W, Kholodilov N, Vila M, et al. Resistance of alpha - synuclein null mice to the parkinsonian neurotoxin MPTP. Proc Natl Acad Sci USA 2002; 99: 14524-9.
163. Przedborski S, Vila M. MPTP: a review of its mechanisms of neurotoxicity. Clin Neurosci Res 2001; 1:407-18.
164. Vila M, Vukosavic S, Jackson-Lewis V, Neystat M, Jakowec M, Przedborski S. Alpha-synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP. J Neurochem 2000; 74: 721-9.
165. Burke RE. Inhibition of mitogen-activated protein kinase and stimulation of Akt kinase signaling pathways: Two approaches with therapeutic potential in the treatment of neurodegenerative disease. Pharmacol Ther 2007; 114: 261-77.
166. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor íon channels. Pharmacol 1999; 51: 7-61.
167. Greenamyre JT, Porter RH. Anatomy and physiology of glutamate in the CNS. Neurology 1994; Suppl 44: 7-13.
168. Olney JW. Excitotoxicity: an overview. Can Dis Wkly Rep 1990; Suppl 16: 47-57.
169. Mattson MP. Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders. Antioxid Redox Signal 2006; 8: 1997-2006.
170. Molz S, Decker H, Dal-Cim T, et al. Glutamate-induced toxicity in hippocampal slices involves apoptotic features and p38 MAPK sig- naling. Neurochem Res 2008; 33: 27-36.
171. Schousboe A, Waagepetersen HS. Role of astrocytes in glutamate homeostasis: implications for excitotoxicity. Neurotox Res 2005; 8: 221-5.
172. Danbolt NC. Glutamate uptake. Prog Neurobiol 2001; 65: 1-105.
173. Blandini F, Nappi G, Tassorelli C, Martignoni E. Functional changes of the basal ganglia circuitry in Parkinson's disease. Prog Neurobiol 2000; 62: 63-88.
174. Chatha BT, Bernard V, Streit P, Bolam JP. Synaptic localization of ionotropic glutamate receptors in the rat substantia nigra. Neurosci-ence 2000; 101: 1037-51.
175. Groenewegen HJ, Berendse HW. Connections of the subthalamic nucleus with ventral striatopallidal parts of the basal ganglia in the rat. J Comp Neurol 1990; 294: 607-22.
176. Kita H, Kitai ST. Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method. J Comp Neurol 1987; 260: 435-52.
177. Blandini F, Porter RH, Greenamyre JT. Glutamate and Parkinson's disease. Mol Neurobiol 1996; 12: 73-94.
178. Difazio MC, Hollingsworth Z, Young AB, PenneyJr JB. Glutamate receptors in the substantia nigra of Parkinson's disease brains. Neu-rology 1992; 42: 402-6.
179. Rodriguez MC, Obeso JA, Olanow CW. Subthalamic nucleus- mediated excitotoxicity in Parkinson's disease: a target for neuro-protection. Ann Neurol 1998; Supp 44: 175-88.
180. Vila M, Ramonet D, Periert C. Mithocondrial alterations in Parkin-son's disease: new clues. J. Neurochem 2008; 107: 317-328.
181. Griffith HR, Okonkwo OC, O'Brien T, Den Hollander JA. Re-duced brain glutamate in patients with Parkinson's disease. NMR Biomed 2008; 21: 381-7.
182. Kashani A, Betancur C, Giros B, Hirsch E, El Mestikawy S. Al-tered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiol Aging 2007; 28: 568-78.
183. Altar CA, Vawter MP, Ginsberg SD. Target identification for CNS diseases by transcriptional profiling. Neuropsychopharmacology 2009; 34(1):18-54.
184. Meredith GE, Totterdell S, Potashkin JA, Surmeier DJ. Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol. Parkinsonism Relat Disord 2008; Suppl 14 2:S112-5.
185. Meredith GE, Totterdell S, Beales M, Meshul CK. Impaired gluta-mate homeostasis and programmed cell death in a chronic MPTP mouse model of Parkinson's disease. Exp Neurol 2009; 219: 334-40.
186. Chassain C, Bielicki G, Keller C, Renou J, Durif F. Metabolic changes detected in vivo by 1H MRS in the MPTP-intoxicated mouse NMR. Biomed 2010; 23: 547-53.
187. Klockgether T, Turski L, Honore T, et al. The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys. Ann Neurol 1991; 30: 717-23.
188. Starr MS. Antiparkinsonian actions of glutamate antagonists-alone and with L-DOPA: a review of evidence and suggestions for possible mechanisms. J Neural Transm Park Dis Dement 1995; 10: 141-85.
189. Battaglia G, Busceti CL, Pontarelli F, et al. Protective role of group-II metabotropic glutamate receptors against nigro-striatal de-generationinducedby1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Neuropharmacology 2003; 45: 155-66.
190. Corti C, Battaglia G, Molinaro G, et al. The use of knock-out mice unravels distinct roles for mGlu2 and mGlu3 metabotropic gluta-mate receptors in mechanisms of neurodegeneration/ neuroprotec-tion. J Neurosci 2007; 27: 8297-308.
191. Battaglia G, Busceti CL, Molinaro G, et al. Endogenous activation of mGlu5 metabotropic glutamate receptors contributes to the de-velopment of nigro-striatal damage induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. J Neurosci 2004; 24: 828-35.
192. Breysse N, Baunez C, Spooren W, Gasparini F, Amalric M. Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism. J Neurosci 2002; 22: 5669-78.
193. Prediger RD. Effects of caffeine in Parkinson's disease: from neuroprotection to the management of motor and non-motor symp-toms. J Alzheimers Dis 2010; 20 Suppl 1: S205-20.
194. Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000; 283: 2674-9.
195. Ascherio A, Zhang SM, Hernan MA, et al. Prospective study of caffeine consumption and risk of Parkinson's disease in men and women. Ann Neurol 2001; 50: 56-63.
196. Saaksjarvi K, Knekt P, Rissanen H, Laaksonen MA, Reunanen A, Mannisto S. Prospective study of coffee consumption and risk of Parkinson's disease. Eur J Clin Nutr 2008; 62: 908-15.
197. Chen JF, Xu K, Petzer JP, et al. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease. J Neurosci 2001; 21: RC143.
198. Kalda A, Yu L, Oztas E, Chen JF. Novel neuroprotection by caf-feine and adenosine A(2A) receptor antagonists in animal models of Parkinson's disease. J Neurol Sci 2006; 248: 9-15.
199. Pierri M, Vaudano E, Sager T, Englund U. KW-6002 protects from MPTP induced dopaminergic toxicity in the mouse. Neuropharma-cology 2005; 48: 517-4.
200. Ikeda K, Kurokawa M, Aoyama S, Kuwana Y. Neuroprotection by adenosine A2A receptor blockade in experimental models of Park-inson's disease. J Neurochem 2002; 80: 262-70.
201. Bara-Jimenez W, Sherzai A, Dimitrova T, et al. Adenosine A(2A) receptor antagonist treatment of Parkinson's disease. Neurology 2003; 61: 293-6.
202. Hauser RA, Hubble JP, Truong DD. Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology 2003; 61: 297-303.
203. Takahashi RN, Pamplona FA, Prediger RD. Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Front Biosci 2008; 13: 2614-32.
204. Mandel S, Youdim MB. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med 2004; 37: 304-17.
205. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracel-lular targets. Eur J Pharmacol 2006; 545: 51-64.
206. Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci 2005; 78: 431-41.
207. Nardi GM, Felippi R, DalBó S, et al. Anti-inflammatory and antioxidant effects of Croton celtidifolius bark. Phytomedicine 2003; 10: 176-84.
208. Nardi GM, Siqueira-Junior JM, Delle Monache F, et al. Antioxi-dant and anti-inflammatory effects of products from Croton celtidi-folius Bailon on carrageenan-induced pleurisy in rats. Phytomedi-cine 2007; 14: 115-22.
209. DalBó S, Jurgensen S, Horst H, et al. Antinociceptive effect of proanthocyanidins from Croton celtidifolius bark. J Pharm Pharma-col 2005; 57: 765-71.
210. DalBó S, Jurgensen S, Horst H, et al. Analysis of the antinocicep-tive effect of the proanthocyanidin-rich fraction obtained from Cro-ton celtidifolius barks: evidence for a role of the dopaminergic sys-tem. Pharmacol Biochem Behav 2006; 85: 317-23.
211. Moreira EL, Rial D, Duarte FS, et al. Central nervous system activity of the proanthocyanidin-rich fraction obtained from Croton celtidifolius in rats. J Pharm Pharmacol 2010; 62: 1061-8.
212. Schroeder EK, Kelsey NA, Doyle J, et al. Green tea epigallocate-chin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal 2009; 11: 469-80.