Neurobiologia do parkinsonismo: II. modelos experimentais

Ponzoni, Silvia; Garcia-Cairasco, Noberto

doi:10.1590/S0004-282X1995000400028

Resumos

O emprego de modelos experimentais de parkinsonismo tem contribuído não só para explicar o conhecimento das funções dos gânglios basais como também tem permitido o surgimento de várias hipóteses para explicar os processos neurodegeneratives do sistema nervoso central. Nesta revisão são apresentados e discutidos os modelos de parkinsonismo que utilizam neurotoxins como a 6-hidroxidopamina, MPTP e o manganês.

parkinsonismo; 6-hidroxidopamina; MPTP; manganês; modelos experimentais

The study of experimental models of parkinsonism has contributed to the knowledge of basal ganglia functions, as well as to the establishment of several hypothesis for the explanation of the cause and expression of central neurodegenerative disorders. In this review we present and discuss several models such as 6-hydroxydopamine, MPTP and manganese, all of them widely used to characterize the behavioral, cellular and molecular mechanisms of parkinsonism.

parkinsonism; 6-hydroxydopamine; MPTP; manganese; experimental models

Neurobiologia do parkinsonismo. II. modelos experimentais

Neurobiology of parkinsonism: II. experimental models

Silvia Ponzoni^I; Noberto Garcia-Cairasco^II

^IDoutor em Ciências, Disciplina de Biofísica do Departamento de Ciências Fisiológicas da Universidade Estadual de Londrina (UEL)

^IIDoutor em Ciências, Laboratório de Neurofisiologia e Neuroetologia Experimental da Disciplina de Neurofisiologia do Departamento de Fisiologia da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (USP)

RESUMO

O emprego de modelos experimentais de parkinsonismo tem contribuído não só para explicar o conhecimento das funções dos gânglios basais como também tem permitido o surgimento de várias hipóteses para explicar os processos neurodegeneratives do sistema nervoso central. Nesta revisão são apresentados e discutidos os modelos de parkinsonismo que utilizam neurotoxins como a 6-hidroxidopamina, MPTP e o manganês.

Palavras-chave:parkinsonismo, 6-hidroxidopamina, MPTP, manganês, modelos experimentais.

SUMMARY

The study of experimental models of parkinsonism has contributed to the knowledge of basal ganglia functions, as well as to the establishment of several hypothesis for the explanation of the cause and expression of central neurodegenerative disorders. In this review we present and discuss several models such as 6-hydroxydopamine, MPTP and manganese, all of them widely used to characterize the behavioral, cellular and molecular mechanisms of parkinsonism.

Key words:parkinsonism, 6-hydroxydopamine, MPTP, manganese, experimental models.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Aceite: 3-maio-1995.

Dra. Sílvia Ponzoni - Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina - Campus Universitário - 86051-970 Londrina PR - Brasil. Fax (043) 327 6932.

1. Biagini.G, Ferraguti F, Ponzoni S, Zoli M, Alboni L, Toffano G, Fuxe K Agnati LF. Neurochemical and behavioural studies on L-DOPA toxicity in the model of manganese lesioned nigrostriatal pathway in the rat: evidence for a protective effect of the GM 1 lactone siagoside. In Fuxe K, Agnati LF, Bjelke B, Ohoson D (eds).Wenner-Gren Symposium on Trophic regulation of the basal ganglia: focus on dopamine neurons. 1994, p 381-407.
2. Brouillet EP, Shinobu L, McGarvey U, Hochberg F, Beal MF. Manganese injection into the rat striatum produces excitotoxic lesions by imparing energy metabolism. Exp Neurol 1993, 120:89-94.
3. Burns RS. Subclinical damage to the nigrostriatal dopamine system by MPTP as a model of preclinical Parkinson's disease: a review. Acta Neurol Scand 1991, 84 (Suppl 136):29-36.
4. Cerruti C, Drian MJ, Kamenka JM Privat A. Protection by BTCP of cultured dopaminergic neurons exposed to neurotoxins. Brain Res 1993, 617:138-142.
5. Donaldson J, McGregor D, LaBella F. Manganese neurotoxicity: a model for free radical mediated neurodegeneration? Can J Physiol Pharmacol 1982, 60:1398-1405.
6. Fahn S, Cohen G. The oxidative stress hypothesis in Parkinson's disease: evidence suppporting it. Ann Neurol 1992, 32:804-812.
7. Ferraz HB, Bertolucci PHF, Pereira JS, Lima JGC, Andrade LAF. Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication. Neurology 1988, 38:550-553.
8. Fornstedt B, Pileblad E, Carlsson A. In vivo autoxidation of dopamine in guinea pig striatum increases with age. J Neurochem 1990, 55:655-659.
9. Flint Beal M, Hyman BT, Koroshetz W. Do effects in mitochondrial energy metabolism underlie the pathophysiology of neurodegenerative diseases? TINS 1993, 16:125-131.
10. Floyd RA, Carney JM. Free radical damage to protein and DNA: mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann Neurol 1992, 32:S22-S27.
11. Glover V, Sandler M. Monoamine oxidase and the brain. Rev Neurosci 1987, 1:145-156.
12. Graham DG, Tiffany SM, Bell WR Jr, Gutknecht WF. Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C 1300 neuroblastoma cells in vitro. Molec Pharmacol 1978, 14:644-653.
13. Graham DG. Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson's disease. Neurotoxicology 1984,5:83-96.
14. Heikkila R, Cohen G. Inhibition of biogenic amine uptake by hydrogen peroxide: a mechanism for toxic effects of 6-hydroxydopamine. Science 1972, 172:1257-1258.
15. Heikkila RE, Hess A, Duvoisin RC. Dopaminergic neurotoxicity of l-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine in mice. Science 1984, 224:1451-1453.
16. Javoy-Agid F, Hirsch EC, Dumas S, Duyckaerts C, Mallet J, Agid Y. Decreased tyrosine hydroxylase messenger RNA in the surviving dopamine neurons of the substantia nigra in Parkinson's disease: an in situ hybridization study. Neuroscience 1990, 38:248-253.
17. Jenkins R, O'Shea R, Thomas KL, Hunt SP. c-jun expression in substantia nigra neurons following striatal 6-hydroxydopamine lesions in the rat. Neuroscience 1993, 53:447-455.
18. Jolicoeur FB, Rivest R. Rodent models of Parkinson's disease In: Boulton AA, Baker GA, Butterworth RF (eds). Animal models of neurological disease: I. Neurodegenerative diseases. Humana Press, 1992, p 135-158.
19. Kastner A, Hirsch EC, Lejeune O, Javoy-Agid F, Rascol O, Agid Y. Is the vulnerability of neurons in the substantia nigra of patients with Parkinson's disease related to their neuromelanin content? J Neurochem 1992, 59:1080-1089.
20. Kumar MVS, Desiraju T. Effects of chronic manganese exposure on rat brain regional biogenic amines and GABA/glutamate system. Biog Amines 1992, 8:79-83.
21. Kurth JH, Kurth MC, Poduslo SE, Schwankhaus JD. Association of a monoamine oxidase B allele with Parkinson's disease. Ann Neurol 1993, 33:368-372.
22. Lange KW. Behavioural effects and supersensitivity in the rat following intranigral MPTP and MPP+ administration. Eur J Phamacol 1990, 175:57-61.
23. Luthman J, Friedemann M, Bickford P, Olson L, Hoffer BJ, Gerhardt GA. In vivo electrochemical measurements and electrophysiological studies of rat striatum following neonatal 6-hydroxydopamine treatment. Neuroscience 1993, 52:677-687.
24. Parenti M, Flauto C, Parati E, Vescovi A, Groppetti A. Manganese neurotoxicity: effects of L-dopa and pargyline treatments. Brain Res 1986, 367:8-13.
25. Pasinetti GM, Osterburg HH, Kelly AB, Kohama S, Morgan DG, Reinhard JF Jr., Stellwagen RH, Finch CE. Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for aging. Molec Brain Res 1992, 13:63-73.
26. Segovia J, Tillakaratne NJK, Whelan K, Tobin AJ, Gale K. Parallel increase in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway. Brain Res 1990, 529:345-348.
27. Stone R. Guam: deadly disease dying out. Science 1993, 261:424-426.
28. Tanner CM. The role of environmental toxins in the etiology of the Parkinson's disease. TINS 1989, 12:49-54.
29. Tetrud JW, Langston JW. MPTP-induced parkinsonism a model for Parkinson's disease. Acta Neurol Scand 1989, 126:35-40.
30. Tripton KF, Singer TP. Advances in our understanding of the mechanisms of the neurotoxicity of MPTP and related compounds. J Neurochem 1993, 61:1191-1206.
31. Ungerstedt U. Post-synaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand 1971 Suppl, 367:69-93.
32. Zigmond MJ, Stricker EM. Animals models of parkinsonism using selective neurotoxins: clinical and basic implications. Internat Rev Neurobiol 1989, 31:1-79.
33. Wang JD, Huang CC, Wang YHH, Chiang JR, Lin JM, Chen JS. Manganese induced parkinsonism: an outbreak due to an unrepaired ventilation control system in a ferromanganese smelter. Brit J Industr Med 1989, 46:856-859.

Datas de Publicação

Publicação nesta coleção
21 Dez 2010
Data do Fascículo
Set 1995

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Biagini.G, Ferraguti F, Ponzoni S, Zoli M, Alboni L, Toffano G, Fuxe K Agnati LF. Neurochemical and behavioural studies on L-DOPA toxicity in the model of manganese lesioned nigrostriatal pathway in the rat: evidence for a protective effect of the GM 1 lactone siagoside. In Fuxe K, Agnati LF, Bjelke B, Ohoson D (eds).Wenner-Gren Symposium on Trophic regulation of the basal ganglia: focus on dopamine neurons. 1994, p 381-407.

[2] 2. Brouillet EP, Shinobu L, McGarvey U, Hochberg F, Beal MF. Manganese injection into the rat striatum produces excitotoxic lesions by imparing energy metabolism. Exp Neurol 1993, 120:89-94.

[3] 3. Burns RS. Subclinical damage to the nigrostriatal dopamine system by MPTP as a model of preclinical Parkinson's disease: a review. Acta Neurol Scand 1991, 84 (Suppl 136):29-36.

[4] 4. Cerruti C, Drian MJ, Kamenka JM Privat A. Protection by BTCP of cultured dopaminergic neurons exposed to neurotoxins. Brain Res 1993, 617:138-142.

[5] 5. Donaldson J, McGregor D, LaBella F. Manganese neurotoxicity: a model for free radical mediated neurodegeneration? Can J Physiol Pharmacol 1982, 60:1398-1405.

[6] 6. Fahn S, Cohen G. The oxidative stress hypothesis in Parkinson's disease: evidence suppporting it. Ann Neurol 1992, 32:804-812.

[7] 7. Ferraz HB, Bertolucci PHF, Pereira JS, Lima JGC, Andrade LAF. Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication. Neurology 1988, 38:550-553.

[8] 8. Fornstedt B, Pileblad E, Carlsson A. In vivo autoxidation of dopamine in guinea pig striatum increases with age. J Neurochem 1990, 55:655-659.

[9] 9. Flint Beal M, Hyman BT, Koroshetz W. Do effects in mitochondrial energy metabolism underlie the pathophysiology of neurodegenerative diseases? TINS 1993, 16:125-131.

[10] 10. Floyd RA, Carney JM. Free radical damage to protein and DNA: mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann Neurol 1992, 32:S22-S27.

[11] 11. Glover V, Sandler M. Monoamine oxidase and the brain. Rev Neurosci 1987, 1:145-156.

[12] 12. Graham DG, Tiffany SM, Bell WR Jr, Gutknecht WF. Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C 1300 neuroblastoma cells in vitro. Molec Pharmacol 1978, 14:644-653.

[13] 13. Graham DG. Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson's disease. Neurotoxicology 1984,5:83-96.

[14] 14. Heikkila R, Cohen G. Inhibition of biogenic amine uptake by hydrogen peroxide: a mechanism for toxic effects of 6-hydroxydopamine. Science 1972, 172:1257-1258.

[15] 15. Heikkila RE, Hess A, Duvoisin RC. Dopaminergic neurotoxicity of l-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine in mice. Science 1984, 224:1451-1453.

[16] 16. Javoy-Agid F, Hirsch EC, Dumas S, Duyckaerts C, Mallet J, Agid Y. Decreased tyrosine hydroxylase messenger RNA in the surviving dopamine neurons of the substantia nigra in Parkinson's disease: an in situ hybridization study. Neuroscience 1990, 38:248-253.

[17] 17. Jenkins R, O'Shea R, Thomas KL, Hunt SP. c-jun expression in substantia nigra neurons following striatal 6-hydroxydopamine lesions in the rat. Neuroscience 1993, 53:447-455.

[18] 18. Jolicoeur FB, Rivest R. Rodent models of Parkinson's disease In: Boulton AA, Baker GA, Butterworth RF (eds). Animal models of neurological disease: I. Neurodegenerative diseases. Humana Press, 1992, p 135-158.

[19] 19. Kastner A, Hirsch EC, Lejeune O, Javoy-Agid F, Rascol O, Agid Y. Is the vulnerability of neurons in the substantia nigra of patients with Parkinson's disease related to their neuromelanin content? J Neurochem 1992, 59:1080-1089.

[20] 20. Kumar MVS, Desiraju T. Effects of chronic manganese exposure on rat brain regional biogenic amines and GABA/glutamate system. Biog Amines 1992, 8:79-83.

[21] 21. Kurth JH, Kurth MC, Poduslo SE, Schwankhaus JD. Association of a monoamine oxidase B allele with Parkinson's disease. Ann Neurol 1993, 33:368-372.

[22] 22. Lange KW. Behavioural effects and supersensitivity in the rat following intranigral MPTP and MPP+ administration. Eur J Phamacol 1990, 175:57-61.

[23] 23. Luthman J, Friedemann M, Bickford P, Olson L, Hoffer BJ, Gerhardt GA. In vivo electrochemical measurements and electrophysiological studies of rat striatum following neonatal 6-hydroxydopamine treatment. Neuroscience 1993, 52:677-687.

[24] 24. Parenti M, Flauto C, Parati E, Vescovi A, Groppetti A. Manganese neurotoxicity: effects of L-dopa and pargyline treatments. Brain Res 1986, 367:8-13.

[25] 25. Pasinetti GM, Osterburg HH, Kelly AB, Kohama S, Morgan DG, Reinhard JF Jr., Stellwagen RH, Finch CE. Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for aging. Molec Brain Res 1992, 13:63-73.

[26] 26. Segovia J, Tillakaratne NJK, Whelan K, Tobin AJ, Gale K. Parallel increase in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway. Brain Res 1990, 529:345-348.

[27] 27. Stone R. Guam: deadly disease dying out. Science 1993, 261:424-426.

[28] 28. Tanner CM. The role of environmental toxins in the etiology of the Parkinson's disease. TINS 1989, 12:49-54.

[29] 29. Tetrud JW, Langston JW. MPTP-induced parkinsonism a model for Parkinson's disease. Acta Neurol Scand 1989, 126:35-40.

[30] 30. Tripton KF, Singer TP. Advances in our understanding of the mechanisms of the neurotoxicity of MPTP and related compounds. J Neurochem 1993, 61:1191-1206.

[31] 31. Ungerstedt U. Post-synaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand 1971 Suppl, 367:69-93.

[32] 32. Zigmond MJ, Stricker EM. Animals models of parkinsonism using selective neurotoxins: clinical and basic implications. Internat Rev Neurobiol 1989, 31:1-79.

[33] 33. Wang JD, Huang CC, Wang YHH, Chiang JR, Lin JM, Chen JS. Manganese induced parkinsonism: an outbreak due to an unrepaired ventilation control system in a ferromanganese smelter. Brit J Industr Med 1989, 46:856-859.