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Parkinson’s Disease
Volume 2011 (2011), Article ID 612989, 14 pages
http://dx.doi.org/10.4061/2011/612989
Research Article

Manganese Inhalation as a Parkinson Disease Model

Laboratorio de Neuromorfologia, Facultad de Estudios Superiores Iztacala, UNAM, Avenida de los Barrios 1, Los Reyes Iztacala, 54090 Tlalnepantla, Edo Mex, Mexico

Received 16 September 2010; Accepted 13 October 2010

Academic Editor: Yuzuru Imai

Copyright © 2011 José Luis Ordoñez-Librado et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. E. Lang and A. M. Lozano, “Parkinson's disease: first of two parts,” New England Journal of Medicine, vol. 339, no. 16, pp. 1130–1143, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. S. B. Dunnett and A. Björklund, “Prospects for new restorative and neuroprotective treatments in Parkinson's disease,” Nature, vol. 399, supplement 6738, pp. A32–A39, 1999. View at Google Scholar · View at Scopus
  3. C. W. Olanow and W. G. Tatton, “Etiology and pathogenesis of Parkinson's disease,” Annual Review of Neuroscience, vol. 22, pp. 123–144, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. R. Betarbet, T. B. Sherer, and J. T. Greenamyre, “Animal models of Parkinson's disease,” BioEssays, vol. 24, no. 4, pp. 308–318, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. M. E. Emborg, “Evaluation of animal models of Parkinson's disease for neuroprotective strategies,” Journal of Neuroscience Methods, vol. 139, no. 2, pp. 121–143, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. D. G. Cook, S. Fahn, and K. A. Brait, “Chronic manganese intoxication,” Archives of Neurology, vol. 30, no. 1, pp. 59–64, 1974. View at Google Scholar · View at Scopus
  7. D. B. Calne, N. S. Chu, C. C. Huang, C. S. Lu, and W. Olanow, “Manganism and idiopathic parkinsonism: similarities and differences,” Neurology, vol. 44, no. 9, pp. 1583–1586, 1994. View at Google Scholar · View at Scopus
  8. P. K. Pal, A. Samii, and D. B. Calne, “Manganese neurotoxicity: a review of clinical features, imaging and pathology,” NeuroToxicology, vol. 20, no. 2-3, pp. 227–238, 1999. View at Google Scholar · View at Scopus
  9. J. Couper, “On the effects of black oxide of manganese when inhaled in the lungs,” British Annals of Medicine, vol. 1, pp. 41–42, 1837. View at Google Scholar
  10. C. C. Huang, “Parkinsonism induced by chronic manganese intoxication—an experience in Taiwan,” Chang Gung Medical Journal, vol. 30, no. 5, pp. 385–395, 2007. View at Google Scholar · View at Scopus
  11. R. M. A. De Bie, R. M. Gladstone, A. P. Strafella, J. H. Ko, and A. E. Lang, “Manganese-induced parkinsonism associated with methcathinone (Ephedrone) abuse,” Archives of Neurology, vol. 64, no. 6, pp. 886–889, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. M. Yamada, S. Ohno, and I. Okayasu, “Chronic manganese poisoning: a neuropathological study with determination of manganese distribution in the brain,” Acta Neuropathologica, vol. 70, no. 3-4, pp. 273–278, 1986. View at Google Scholar
  13. B. A. Racette, L. McGee-Minnich, S. M. Moerlein, J. W. Mink, T. O. Videen, and J. S. Perlmutter, “Welding-related parkinsonism: clinical-features, treatment, and pathophysiology,” Neurology, vol. 56, no. 1, pp. 8–13, 2001. View at Google Scholar · View at Scopus
  14. H. Eriksson, K. Mägiste, L. O. Plantin et al., “Effects of manganese oxide on monkeys as revealed by a combined neurochemical, histological and neurophysiological evaluation,” Archives of Toxicology, vol. 61, no. 1, pp. 46–52, 1987. View at Google Scholar · View at Scopus
  15. H. Eriksson, J. Tedroff, K. A. Thuomas et al., “Manganese induced brain lesions in Macaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging,” Archives of Toxicology, vol. 66, no. 6, pp. 403–407, 1992. View at Publisher · View at Google Scholar · View at Scopus
  16. T. R. Guilarte, N. C. Burton, J. L. McGlothan et al., “Impairment of nigrostriatal dopamine neurotransmission by manganese is mediated by pre-synaptic mechanism(s): implications to manganese-induced parkinsonism,” Journal of Neurochemistry, vol. 107, no. 5, pp. 1236–1247, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. T. R. Guilarte, M. K. Chen, J. L. McGlothan et al., “Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human primates,” Experimental Neurology, vol. 202, no. 2, pp. 381–390, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. M. F. Struve, B. E. McManus, B. A. Wong, and D. C. Dorman, “Basal ganglia neurotransmitter concentrations in rhesus monkeys following subchronic manganese sulfate inhalation,” American Journal of Industrial Medicine, vol. 50, no. 10, pp. 772–778, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. E. Bonilla, “L-tyrosine hydroxylase activity in the rat brain after chronic oral administration of manganese chloride,” Neurobehavioral Toxicology and Teratology, vol. 2, no. 1, pp. 37–41, 1980. View at Google Scholar · View at Scopus
  20. S. V. Chandra and G. S. Shukla, “Concentrations of striatal catecholamines in rats given manganese chloride through drinking water,” Journal of Neurochemistry, vol. 36, no. 2, pp. 683–687, 1981. View at Google Scholar · View at Scopus
  21. N. Autissier, L. Rochette, and P. Dumas, “Dopamine and norepinephrine turnover in various regions of the rat brain after chronic manganese chloride administration,” Toxicology, vol. 24, no. 2, pp. 175–182, 1982. View at Publisher · View at Google Scholar
  22. G. Gianutsos and M. T. Murray, “Alterations in brain dopamine and GABA following inorganic or organic manganese administration,” NeuroToxicology, vol. 3, no. 3, pp. 75–81, 1982. View at Google Scholar · View at Scopus
  23. X. Liu, K. A. Sullivan, J. E. Madl, M. Legare, and R. B. Tjalkens, “Manganese-induced neurotoxicity: the role of astroglial-derived nitric oxide in striatal interneuron degeneration,” Toxicological Sciences, vol. 91, no. 2, pp. 521–531, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. C. W. Olanow, P. F. Good, H. Shinotoh et al., “Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study,” Neurology, vol. 46, no. 2, pp. 492–498, 1996. View at Google Scholar · View at Scopus
  25. L. Normandin, M. Panisset, and J. Zayed, “Manganese neurotoxicity: behavioral, pathological, and biochemical effects following various routes of exposure,” Reviews on Environmental Health, vol. 17, no. 3, pp. 189–217, 2002. View at Google Scholar · View at Scopus
  26. D. C. Dorman, M. F. Struve, H. J. Clewell, and M. E. Andersen, “Application of pharmacokinetic data to the risk assessment of inhaled manganese,” NeuroToxicology, vol. 27, no. 5, pp. 752–764, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. M. Thiruchelvam, E. K. Richfield, R. B. Baggs, A. W. Tank, and D. A. Cory-Slechta, “The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson's disease,” Journal of Neuroscience, vol. 20, no. 24, pp. 9207–9214, 2000. View at Google Scholar · View at Scopus
  28. M. K. Chen, J. S. Lee, J. L. McGlothan et al., “Acute manganese administration alters dopamine transporter levels in the non-human primate striatum,” NeuroToxicology, vol. 27, no. 2, pp. 229–236, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. R. T. Ingersoll, E. B. Montgomery, and H. V. Aposhian, “Central nervous system toxicity of manganese II: cocaine or reserpine inhibit manganese concentration in the rat brain,” NeuroToxicology, vol. 20, no. 2-3, pp. 467–476, 1999. View at Google Scholar · View at Scopus
  30. K. M. Erikson, C. E. John, S. R. Jones, and M. Aschner, “Manganese accumulation in striatum of mice exposed to toxic doses is dependent upon a functional dopamine transporter,” Environmental Toxicology and Pharmacology, vol. 20, no. 3, pp. 390–394, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. J. G. Anderson, P. T. Cooney, and K. M. Erikson, “Inhibition of DAT function attenuates manganese accumulation in the globus pallidus,” Environmental Toxicology and Pharmacology, vol. 23, no. 2, pp. 179–184, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. C. E. Gavin, K. K. Gunter, and T. E. Gunter, “Mn2+ sequestration by mitochondria and inhibition of oxidative phosphorylation,” Toxicology and Applied Pharmacology, vol. 115, no. 1, pp. 1–5, 1992. View at Publisher · View at Google Scholar · View at Scopus
  33. E. F. Soliman, W. Slikker, and S. F. Ali, “Manganese-induced oxidative stress as measured by a fluorescent probe: an in vitro study,” Neuroscience Research Communications, vol. 17, no. 3, pp. 185–193, 1995. View at Google Scholar · View at Scopus
  34. J. Donaldson, D. McGregor, and F. LaBella, “Manganese neurotoxicity: a model for free radical mediated neurodegeneration,” Canadian Journal of Physiology and Pharmacology, vol. 60, no. 11, pp. 1398–1405, 1982. View at Google Scholar · View at Scopus
  35. T. M. Florence and J. L. Stauber, “Manganese catalysis of dopamine oxidation,” Science of the Total Environment, vol. 78, pp. 233–240, 1989. View at Publisher · View at Google Scholar · View at Scopus
  36. W. N. Sloot, J. Korf, J. F. Koster, L. E. A. De Wit, and J. B. P. Gramsbergen, “Manganese-induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo,” Experimental Neurology, vol. 138, no. 2, pp. 236–245, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. B. Xu, Z. F. Xu, and Y. Deng, “Manganese exposure alters the expression of N-methyl-D-aspartate receptor subunit mRNAs and proteins in rat striatum,” Journal of Biochemical and Molecular Toxicology, vol. 24, no. 1, pp. 1–9, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. E. P. Brouillet, L. Shinobu, U. McGarvey, F. Hochberg, and M. F. Beal, “Manganese injection into the rat striatum produces excitotoxic lesions by impairing energy metabolism,” Experimental Neurology, vol. 120, no. 1, pp. 89–94, 1993. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. A. J. Daniels and J. Abarca, “Effect of intranigral Mn on striatal and nigral synthesis and levels of dopamine and cofactor,” Neurotoxicology and Teratology, vol. 13, no. 5, pp. 483–487, 1991. View at Publisher · View at Google Scholar · View at Scopus
  40. G. Díaz-Véliz, S. Mora, P. Gómez et al., “Behavioral effects of manganese injected in the rat substantia nigra are potentiated by dicumarol, a DT-diaphorase inhibitor,” Pharmacology Biochemistry and Behavior, vol. 77, no. 2, pp. 245–251, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. A. B. Santamaria and S. I. Sulsky, “Risk assessment of an essential element: manganese,” Journal of Toxicology and Environmental Health. Part A, vol. 73, no. 2-3, pp. 128–155, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. P. Calabresi, M. Ammassari-Teule, P. Gubellini et al., “A synaptic mechanism underlying the behavioral abnormalities induced by manganese intoxication,” Neurobiology of Disease, vol. 8, no. 3, pp. 419–432, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. C. W. Olanow, “Manganese-induced parkinsonism and parkinson's disease,” Annals of the New York Academy of Sciences, vol. 1012, pp. 209–223, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. D. P. Perl and C. W. Olanow, “The neuropathology of manganese-induced parkinsonism,” Journal of Neuropathology and Experimental Neurology, vol. 66, no. 8, pp. 675–682, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. R. G. Lucchini, C. J. Martin, and B. C. Doney, “From manganism to manganese-induced parkinsonism: a conceptual model based on the evolution of exposure,” NeuroMolecular Medicine, vol. 11, no. 4, pp. 311–321, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. T. R. Guilarte, “Manganese and Parkinson's disease: a critical review and new findings,” Environmental Health Perspectives, vol. 118, no. 8, pp. 1071–1080, 2010. View at Publisher · View at Google Scholar · View at PubMed
  47. C. S. Lu, C. C. Huang, N. S. Chu, and D. B. Calne, “Levodopa failure in chronic manganism,” Neurology, vol. 44, no. 9, pp. 1600–1602, 1994. View at Google Scholar · View at Scopus
  48. M. G. Cersosimo and W. C. Koller, “The diagnosis of manganese-induced parkinsonism,” NeuroToxicology, vol. 27, no. 3, pp. 340–346, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. M. Aschner, K. M. Erikson, E. H. Hernández, and R. Tjalkens, “Manganese and its role in Parkinson's disease: from transport to neuropathology,” NeuroMolecular Medicine, vol. 11, no. 4, pp. 252–266, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. M. Aschner, T. R. Guilarte, J. S. Schneider, and W. Zheng, “Manganese: recent advances in understanding its transport and neurotoxicity,” Toxicology and Applied Pharmacology, vol. 221, no. 2, pp. 131–147, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. R. Gwiazda, R. Lucchini, and D. Smith, “Adequacy and consistency of animal studies to evaluate the neurotoxicity of chronic low-level manganese exposure in humans,” Journal of Toxicology and Environmental Health. Part A, vol. 70, no. 7, pp. 594–605, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. W. N. Sloot, A. J. Van der Sluijs-Gelling, and J. B. P. Gramsbergen, “Selective lesions by manganese and extensive damage by iron after injection into rat striatum or hippocampus,” Journal of Neurochemistry, vol. 62, no. 1, pp. 205–216, 1994. View at Google Scholar · View at Scopus
  53. H. S. Chun, H. Lee, and J. H. Son, “Manganese induces endoplasmic reticulum (ER) stress and activates multiple caspases in nigral dopaminergic neuronal cells, SN4741,” Neuroscience Letters, vol. 316, no. 1, pp. 5–8, 2001. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Zhang, V. A. Fitsanakis, G. Gu et al., “Manganese ethylene-bis-dithiocarbamate and selective dopaminergic neurodegeneration in rat: a link through mitochondrial dysfunction,” Journal of Neurochemistry, vol. 84, no. 2, pp. 336–346, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. S. C. Sistrunk, M. K. Ross, and N. M. Filipov, “Direct effects of manganese compounds on dopamine and its metabolite Dopac: an in vitro study,” Environmental Toxicology and Pharmacology, vol. 23, no. 3, pp. 286–296, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. K. Sriram, G. X. Lin, A. M. Jefferson et al., “Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes,” Archives of Toxicology, vol. 84, no. 7, pp. 521–540, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. M. Tomás-Camardiel, A. J. Herrera, J. L. Venero, M. Cruz Sánchez-Hidalgo, J. Cano, and A. Machado, “Differential regulation of glutamic acid decarboxylase mRNA and tyrosine hydroxylase mRNA expression in the aged manganese-treated rats,” Molecular Brain Research, vol. 103, no. 1-2, pp. 116–129, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. R. H. Gwiazda, D. Lee, J. Sheridan, and D. R. Smith, “Low cumulative manganese exposure affects striatal GABA but not dopamine,” NeuroToxicology, vol. 95, no. 1, pp. 1–8, 2002. View at Google Scholar
  59. M. S. Desole, G. Esposito, R. Migheli et al., “Allopurinol protects against manganese-induced oxidative stress in the striatum and in the brainstem of the rat,” Neuroscience Letters, vol. 192, no. 2, pp. 73–76, 1995. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Segura-Aguilar and C. Lind, “On the mechanism of the Mn-induced neurotoxicity of dopamine: prevention of quinone-derived oxygen toxicity by DT diaphorase and superoxide dismutase,” Chemico-Biological Interactions, vol. 72, no. 3, pp. 309–324, 1989. View at Publisher · View at Google Scholar · View at Scopus
  61. R. A. Yokel, “Manganese flux across the blood-brain barrier,” NeuroMolecular Medicine, vol. 11, no. 4, pp. 297–310, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. A. Takeda, “Manganese action in brain function,” Brain Research Reviews, vol. 41, no. 1, pp. 79–87, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. C. Au, A. Benedetto, and M. Aschner, “Manganese transport in eukaryotes: the role of DMT1,” NeuroToxicology, vol. 29, no. 4, pp. 569–576, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. J. R. Burdo, J. Martin, S. L. Menzies et al., “Cellular distribution of iron in the brain of the Belgrade rat,” Neuroscience, vol. 93, no. 3, pp. 1189–1196, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. A. S. Hazell, “Astrocytes and manganese neurotoxicity,” Neurochemistry International, vol. 41, no. 4, pp. 271–277, 2002. View at Publisher · View at Google Scholar
  66. F. S. Archibald and C. Tyree, “Manganese poisoning and the attack of trivalent manganese upon catecholamines,” Archives of Biochemistry and Biophysics, vol. 256, no. 2, pp. 638–650, 1987. View at Google Scholar
  67. S. F. Ali, H. M. Duhart, G. D. Newport, G. W. Lipe, and W. Slikker, “Manganese-induced reactive oxygen species: comparison between Mn+2 and Mn+3,” Neurodegeneration, vol. 4, no. 3, pp. 329–334, 1995. View at Google Scholar
  68. J. Y. Chen, G. C. Tsao, Q. Zhao, and W. Zheng, “Differential cytotoxicity of Mn(II) and Mn(III): special reference to mitochondrial [Fe-S] containing enzymes,” Toxicology and Applied Pharmacology, vol. 175, no. 2, pp. 160–168, 2001. View at Publisher · View at Google Scholar · View at PubMed
  69. D. HaMai and S. C. Bondy, “Oxidative basis of manganese neurotoxicity,” Annals of the New York Academy of Sciences, vol. 1012, pp. 129–141, 2004. View at Publisher · View at Google Scholar
  70. I. Q. Whishaw, S. M. Pellis, B. P. Gorny, and V. C. Pellis, “The impairments in reaching and the movements of compensation in rats with motor cortex lesions: an endpoint, videorecording, and movement notation analysis,” Behavioural Brain Research, vol. 42, no. 1, pp. 77–91, 1991. View at Publisher · View at Google Scholar
  71. T. D. Farr and I. Q. Whishaw, “Quantitative and qualitative impairments in skilled reaching in the mouse (Mus musculus) after a focal motor cortex stroke,” Stroke, vol. 33, no. 7, pp. 1869–1875, 2002. View at Publisher · View at Google Scholar
  72. T. A. Perry, E. M Torres, C. Czech, K. Beyreuther, S. Richards, and S. B. Dunnett, “Cognitive and motor function in transgenic mice carrying excess copies of the 695 and 751 amino acid isoforms of the amyloid precursor protein gene,” Alzheimer's Research, vol. 1, pp. 5–14, 1995. View at Google Scholar
  73. M. R. Avila-Costa, E. Montiel Flores, L. Colin-Barenque et al., “Nigrostriatal modifications after vanadium inhalation: an immunocytochemical and cytological approach,” Neurochemical Research, vol. 29, no. 7, pp. 1365–1369, 2004. View at Publisher · View at Google Scholar
  74. D. Martinez-Fong, M. G. Rosales, J. L. Gongora-Alfaro, S. Hernandez, and J. Aceves, “NMDA receptor mediates dopamine release in the striatum of unanaesthetized rats as measured by brain microdialysis,” Brain Research, vol. 595, no. 2, pp. 309–315, 1992. View at Publisher · View at Google Scholar
  75. M. M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding,” Analytical Biochemistry, vol. 72, no. 1-2, pp. 248–254, 1976. View at Google Scholar
  76. T. I. Fortoul, R. C. Salgado, S. G. Moncada et al., “Ultrastructural findings in the murine Nonciliated Bronchiolar Cells (NCBC) after subacute inhalation of lead acetate,” Acta Veterinaria Brno, vol. 68, no. 1, pp. 51–55, 1999. View at Google Scholar
  77. J. Biernaskie, G. Chernenko, and D. Corbett, “Efficacy of rehabilitative experience declines with time after focal ischemic brain injury,” Journal of Neuroscience, vol. 24, no. 5, pp. 1245–1254, 2004. View at Publisher · View at Google Scholar · View at PubMed
  78. G. A. S. Metz, T. Farr, M. Ballermann, and I. Q. Whishaw, “Chronic levodopa therapy does not improve skilled reach accuracy or reach range on a pasta matrix reaching task in 6-OHDA dopamine-depleted (hemi-Parkinson analogue) rats,” European Journal of Neuroscience, vol. 14, no. 1, pp. 27–37, 2001. View at Publisher · View at Google Scholar
  79. I. Q. Whishaw, O. Suchowersky, L. Davis, J. Sarna, G. A. Metz, and S. M. Pellis, “Impairment of pronation, supination, and body co-ordination in reach-to-grasp tasks in human Parkinson's disease (PD) reveals homology to deficits in animal models,” Behavioural Brain Research, vol. 133, no. 2, pp. 165–176, 2002. View at Publisher · View at Google Scholar
  80. U. Castiello, K. Bennett, C. Bonfiglioli, S. Lim, and R. F. Peppard, “The reach-to-grasp movement in Parkinson's disease: response to a simultaneous perturbation of object position and object size,” Experimental Brain Research, vol. 125, no. 4, pp. 453–462, 1999. View at Publisher · View at Google Scholar
  81. G. M. Jackson, S. R. Jackson, and J. V. Hindle, “The control of bimanual reach-to-grasp movements in hemiparkinsonian patients,” Experimental Brain Research, vol. 132, no. 3, pp. 390–398, 2000. View at Google Scholar
  82. C. L. MacLellan, S. Gyawali, and F. Colbourne, “Skilled reaching impairments follow intrastriatal hemorrhagic stroke in rats,” Behavioural Brain Research, vol. 175, no. 1, pp. 82–89, 2006. View at Publisher · View at Google Scholar · View at PubMed
  83. F. Garcia-Hernandez, M. T. Pacheco-Cano, and R. Drucker-Colin, “Reduction of motor impairment by adrenal medulla transplant in aged rats,” Physiology and Behavior, vol. 54, no. 3, pp. 589–598, 1993. View at Publisher · View at Google Scholar
  84. N. Ogawa, Y. Hirose, and S. Ohara, “A simple quantitative bradykinesia test in MPTP-treated mice,” Research Communications in Chemical Pathology and Pharmacology, vol. 50, no. 3, pp. 435–441, 1985. View at Google Scholar
  85. P. O. Fernagut, E. Diguet, B. Labattu, and F. Tison, “A simple method to measure stride length as an index of nigrostriatal dysfunction in mice,” Journal of Neuroscience Methods, vol. 113, no. 2, pp. 123–130, 2002. View at Publisher · View at Google Scholar
  86. D. Y. Hwang, S. M. Fleming, P. Ardayfio et al., “3,4-Dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient Aphakia mice: behavioral characterization of a novel genetic model of Parkinson's disease,” Journal of Neuroscience, vol. 25, no. 8, pp. 2132–2137, 2005. View at Publisher · View at Google Scholar · View at PubMed
  87. J. P. Nachtman, R. E. Tubben, and R. L. Commissaris, “Behavioral effects of chronic manganese administration in rats: locomotor activity studies,” Neurobehavioral Toxicology and Teratology, vol. 8, no. 6, pp. 711–715, 1986. View at Google Scholar
  88. G. S. Shukla and R. L. Singhal, “The present status of biological effects of toxic metals in the environment: lead, cadmium, and manganese,” Canadian Journal of Physiology and Pharmacology, vol. 62, no. 8, pp. 1015–1031, 1984. View at Google Scholar
  89. A. Rödter, C. Winkler, M. Samii, and G. Nikkhah, “Complex sensorimotor behavioral changes after terminal striatal 6-OHDA lesion and transplantation of dopaminergic embryonic micrografts,” Cell Transplantation, vol. 9, no. 2, pp. 197–214, 2000. View at Google Scholar
  90. M. D. Lindner, C. K. Cain, M. A. Plone et al., “Incomplete nigrostriatal dopaminergic cell loss and partial reductions in striatal dopamine produce akinesia, rigidity, tremor and cognitive deficits in middle-aged rats,” Behavioural Brain Research, vol. 102, no. 1-2, pp. 1–16, 1999. View at Publisher · View at Google Scholar
  91. M. A. Cenci, I. Q. Whishaw, and T. Schallert, “Animal models of neurological deficits: how relevant is the rat?” Nature Reviews Neuroscience, vol. 3, no. 7, pp. 574–579, 2002. View at Publisher · View at Google Scholar · View at PubMed
  92. T. Schallert, B. F. Petrie, and I. Q. Whishaw, “Neonatal dopamine depletion: spared and unspared sensorimotor and attentional disorders and effects of further depletion in adulthood,” Psychobiology, vol. 17, no. 4, pp. 386–396, 1989. View at Google Scholar
  93. U. Ungerstedt, “Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system,” Acta Physiologica Scandinavica, vol. 367, supplement, pp. 95–122, 1971. View at Google Scholar
  94. M. Morello, A. Canini, P. Mattioli et al., “Sub-cellular localization of manganese in the basal ganglia of normal and manganese-treated rats. An electron spectroscopy imaging and electron energy-loss spectroscopy study,” NeuroToxicology, vol. 29, no. 1, pp. 60–72, 2008. View at Publisher · View at Google Scholar · View at PubMed
  95. T. E. Gunter, C. E. Gavin, M. Aschner, and K. K. Gunter, “Speciation of manganese in cells and mitochondria: a search for the proximal cause of manganese neurotoxicity,” NeuroToxicology, vol. 27, no. 5, pp. 765–776, 2006. View at Publisher · View at Google Scholar · View at PubMed
  96. A. H. Stokes, T. G. Hastings, and K. E. Vrana, “Cytotoxic and genotoxic potential of dopamine,” Journal of Neuroscience Research, vol. 55, no. 6, pp. 659–665, 1999. View at Publisher · View at Google Scholar
  97. A. S. Perumal, V. B. Gopal, W. K. Tordzro, T. B. Cooper, and J. L. Cadet, “Vitamin E attenuates the toxic effects of 6-hydroxydopamine on free radical scavenging systems in rat brain,” Brain Research Bulletin, vol. 29, no. 5, pp. 699–701, 1992. View at Publisher · View at Google Scholar
  98. S. N. Haber, H. Ryoo, C. Cox, and W. Lu, “Subsets of midbrain dopaminergic neurons in monkeys are distinguished by different levels of mRNA for the dopamine transporter: comparison with the mRNA for the D receptor, tyrosine hydroxylase and calbindin immunoreactivity,” Journal of Comparative Neurology, vol. 362, no. 3, pp. 400–410, 1995. View at Publisher · View at Google Scholar · View at PubMed
  99. Y. Hirata, K. Kiuchi, and T. Nagatsu, “Manganese mimics the action of 1-methyl-4-phenylpyridinium ion, a dopaminergic neurotoxin, in rat striatal tissue slices,” Neuroscience Letters, vol. 311, no. 1, pp. 53–56, 2001. View at Google Scholar
  100. G. R. Uhl, “Hypothesis: the role of dopaminergic transporters in selective vulnerability of cells in Parkinson's disease,” Annals of Neurology, vol. 43, no. 5, pp. 555–560, 1998. View at Publisher · View at Google Scholar · View at PubMed
  101. B. J. Ciliax, G. W. Drash, J. K. Staley et al., “Immunocytochemical localization of the dopamine transporter in human brain,” The Journal of Comparative Neurology, vol. 409, no. 1, pp. 38–56, 1999. View at Google Scholar
  102. A. Schober, “Classic toxin-induced animal models of Parkinsons disease: 6-OHDA and MPTP,” Cell and Tissue Research, vol. 318, no. 1, pp. 215–224, 2004. View at Google Scholar
  103. M. S. Goldberg, S. M. Fleming, J. J. Palacino et al., “Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons,” Journal of Biological Chemistry, vol. 278, no. 44, pp. 43628–43635, 2003. View at Publisher · View at Google Scholar · View at PubMed
  104. B. I. Giasson, J. E. Duda, S. M. Quinn, B. Zhang, J. Q. Trojanowski, and V. M. Y. Lee, “Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein,” Neuron, vol. 34, no. 4, pp. 521–533, 2002. View at Publisher · View at Google Scholar
  105. V. W. Yong, T. L. Perry, and W. J. Godolphin, “Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons,” NeuroToxicology, vol. 7, no. 1, pp. 19–24, 1986. View at Google Scholar