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. 2003 Jun;111(8):1065–1073. doi: 10.1289/ehp.6361

Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation.

Bin Liu 1, Hui-Ming Gao 1, Jau-Shyong Hong 1
PMCID: PMC1241555  PMID: 12826478

Abstract

Idiopathic Parkinson's disease (PD) is a devastating movement disorder characterized by selective degeneration of the nigrostriatal dopaminergic pathway. Neurodegeneration usually starts in the fifth decade of life and progresses over 5-10 years before reaching the fully symptomatic disease state. Despite decades of intense research, the etiology of sporadic PD and the mechanism underlying the selective neuronal loss remain unknown. However, the late onset and slow-progressing nature of the disease has prompted the consideration of environmental exposure to agrochemicals, including pesticides, as a risk factor. Moreover, increasing evidence suggests that early-life occurrence of inflammation in the brain, as a consequence of either brain injury or exposure to infectious agents, may play a role in the pathogenesis of PD. Most important, there may be a self-propelling cycle of inflammatory process involving brain immune cells (microglia and astrocytes) that drives the slow yet progressive neurodegenerative process. Deciphering the molecular and cellular mechanisms governing those intricate interactions would significantly advance our understanding of the etiology and pathogenesis of PD and aid the development of therapeutic strategies for the treatment of the disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alafiatayo R. A., Cookson M. R., Pentreath V. W. Production of prostaglandins D2 and E2 by mouse fibroblasts and astrocytes in culture caused by Trypanosoma brucei brucei products and endotoxin. Parasitol Res. 1994;80(3):223–229. doi: 10.1007/BF00932678. [DOI] [PubMed] [Google Scholar]
  2. Alam M., Schmidt W. J. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res. 2002 Oct 17;136(1):317–324. doi: 10.1016/s0166-4328(02)00180-8. [DOI] [PubMed] [Google Scholar]
  3. Ali S. F., Chandra O., Hasan M. Effects of an organophosphate (dichlorvos) on open field behavior and locomotor activity: correlation with regional brain monoamine levels. Psychopharmacology (Berl) 1980;68(1):37–42. doi: 10.1007/BF00426647. [DOI] [PubMed] [Google Scholar]
  4. Ali S. F., Hasan M., Tariq M. Levels of dopamine, norepinephrine & 5-hydroxytryptamine in different regions of rat brain & spinal cord following chronic administration of organophosphate pesticide dichlorvos. Indian J Exp Biol. 1979 Apr;17(4):424–426. [PubMed] [Google Scholar]
  5. Aloisi F. The role of microglia and astrocytes in CNS immune surveillance and immunopathology. Adv Exp Med Biol. 1999;468:123–133. doi: 10.1007/978-1-4615-4685-6_10. [DOI] [PubMed] [Google Scholar]
  6. Altschuler E. Gastric Helicobacter pylori infection as a cause of idiopathic Parkinson disease and non-arteric anterior optic ischemic neuropathy. Med Hypotheses. 1996 Nov;47(5):413–414. doi: 10.1016/s0306-9877(96)90223-6. [DOI] [PubMed] [Google Scholar]
  7. Araki E., Forster C., Dubinsky J. M., Ross M. E., Iadecola C. Cyclooxygenase-2 inhibitor ns-398 protects neuronal cultures from lipopolysaccharide-induced neurotoxicity. Stroke. 2001 Oct;32(10):2370–2375. doi: 10.1161/hs1001.096057. [DOI] [PubMed] [Google Scholar]
  8. Babior B. M. NADPH oxidase: an update. Blood. 1999 Mar 1;93(5):1464–1476. [PubMed] [Google Scholar]
  9. Barbeau A., Dallaire L., Buu N. T., Poirier J., Rucinska E. Comparative behavioral, biochemical and pigmentary effects of MPTP, MPP+ and paraquat in Rana pipiens. Life Sci. 1985 Oct 21;37(16):1529–1538. doi: 10.1016/0024-3205(85)90185-7. [DOI] [PubMed] [Google Scholar]
  10. Barclay A. Neil, Wright Gavin J., Brooke Gary, Brown Marion H. CD200 and membrane protein interactions in the control of myeloid cells. Trends Immunol. 2002 Jun;23(6):285–290. doi: 10.1016/s1471-4906(02)02223-8. [DOI] [PubMed] [Google Scholar]
  11. Barde Y. A. Trophic factors and neuronal survival. Neuron. 1989 Jun;2(6):1525–1534. doi: 10.1016/0896-6273(89)90040-8. [DOI] [PubMed] [Google Scholar]
  12. Barron K. D. The microglial cell. A historical review. J Neurol Sci. 1995 Dec;134 (Suppl):57–68. doi: 10.1016/0022-510x(95)00209-k. [DOI] [PubMed] [Google Scholar]
  13. Beaman L., Beaman B. L. Interactions of Nocardia asteroides with murine glia cells in culture. Infect Immun. 1993 Jan;61(1):343–347. doi: 10.1128/iai.61.1.343-347.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Beckman J. S., Crow J. P. Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans. 1993 May;21(2):330–334. doi: 10.1042/bst0210330. [DOI] [PubMed] [Google Scholar]
  15. Ben-Shlomo Y. The epidemiology of Parkinson's disease. Baillieres Clin Neurol. 1997 Apr;6(1):55–68. [PubMed] [Google Scholar]
  16. Betarbet R., Sherer T. B., MacKenzie G., Garcia-Osuna M., Panov A. V., Greenamyre J. T. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000 Dec;3(12):1301–1306. doi: 10.1038/81834. [DOI] [PubMed] [Google Scholar]
  17. Bhatt M. H., Elias M. A., Mankodi A. K. Acute and reversible parkinsonism due to organophosphate pesticide intoxication: five cases. Neurology. 1999 Apr 22;52(7):1467–1471. doi: 10.1212/wnl.52.7.1467. [DOI] [PubMed] [Google Scholar]
  18. Bhatt M., Desai J., Mankodi A., Elias M., Wadia N. Posttraumatic akinetic-rigid syndrome resembling Parkinson's disease: a report on three patients. Mov Disord. 2000 Mar;15(2):313–317. doi: 10.1002/1531-8257(200003)15:2<313::aid-mds1017>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  19. Blum-Degen D., Müller T., Kuhn W., Gerlach M., Przuntek H., Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett. 1995 Dec 29;202(1-2):17–20. doi: 10.1016/0304-3940(95)12192-7. [DOI] [PubMed] [Google Scholar]
  20. Bougria M., Vitorica J., Cano J., Machado A. Implication of dopamine transporter system on 1-methyl-4-phenylpyridinium and rotenone effect in striatal synaptosomes. Eur J Pharmacol. 1995 Nov 30;291(3):407–415. doi: 10.1016/0922-4106(95)90083-7. [DOI] [PubMed] [Google Scholar]
  21. Brooks A. I., Chadwick C. A., Gelbard H. A., Cory-Slechta D. A., Federoff H. J. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res. 1999 Mar 27;823(1-2):1–10. doi: 10.1016/s0006-8993(98)01192-5. [DOI] [PubMed] [Google Scholar]
  22. Castaño A., Herrera A. J., Cano J., Machado A. Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem. 1998 Apr;70(4):1584–1592. doi: 10.1046/j.1471-4159.1998.70041584.x. [DOI] [PubMed] [Google Scholar]
  23. Chang R. C., Hudson P., Wilson B., Haddon L., Hong J. S. Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia. Brain Res. 2000 Jan 24;853(2):236–244. doi: 10.1016/s0006-8993(99)02255-6. [DOI] [PubMed] [Google Scholar]
  24. Chang R. C., Hudson P., Wilson B., Liu B., Abel H., Hemperly J., Hong J. S. Immune modulatory effects of neural cell adhesion molecules on lipopolysaccharide-induced nitric oxide production by cultured glia. Brain Res Mol Brain Res. 2000 Sep 30;81(1-2):197–201. doi: 10.1016/s0169-328x(00)00175-3. [DOI] [PubMed] [Google Scholar]
  25. Chao C. C., Hu S., Ehrlich L., Peterson P. K. Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain Behav Immun. 1995 Dec;9(4):355–365. doi: 10.1006/brbi.1995.1033. [DOI] [PubMed] [Google Scholar]
  26. Chao C. C., Hu S., Molitor T. W., Shaskan E. G., Peterson P. K. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol. 1992 Oct 15;149(8):2736–2741. [PubMed] [Google Scholar]
  27. Charlett A., Dobbs R. J., Dobbs S. M., Weller C., Brady P., Peterson D. W. Parkinsonism: siblings share Helicobacter pylori seropositivity and facets of syndrome. Acta Neurol Scand. 1999 Jan;99(1):26–35. doi: 10.1111/j.1600-0404.1999.tb00654.x. [DOI] [PubMed] [Google Scholar]
  28. Choksi N. Y., Kodavanti P. R., Tilson H. A., Booth R. G. Effects of polychlorinated biphenyls (PCBs) on brain tyrosine hydroxylase activity and dopamine synthesis in rats. Fundam Appl Toxicol. 1997 Sep;39(1):76–80. doi: 10.1006/faat.1997.2351. [DOI] [PubMed] [Google Scholar]
  29. Chu I., Villeneuve D. C., Yagminas A., Lecavalier P., Håkansson H., Ahlborg U. G., Valli V. E., Kennedy S. W., Bergman A., Seegal R. F. Toxicity of PCB 77 (3,3',4,4'-tetrachlorobiphenyl) and PCB 118 (2,3',4,4'5-pentachlorobiphenyl) in the rat following subchronic dietary exposure. Fundam Appl Toxicol. 1995 Jul;26(2):282–292. doi: 10.1006/faat.1995.1099. [DOI] [PubMed] [Google Scholar]
  30. Chun H. S., Gibson G. E., DeGiorgio L. A., Zhang H., Kidd V. J., Son J. H. Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism. J Neurochem. 2001 Feb;76(4):1010–1021. doi: 10.1046/j.1471-4159.2001.00096.x. [DOI] [PubMed] [Google Scholar]
  31. Corrigan F. M., Murray L., Wyatt C. L., Shore R. F. Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson's disease. Exp Neurol. 1998 Apr;150(2):339–342. doi: 10.1006/exnr.1998.6776. [DOI] [PubMed] [Google Scholar]
  32. Corrigan F. M., Wienburg C. L., Shore R. F., Daniel S. E., Mann D. Organochlorine insecticides in substantia nigra in Parkinson's disease. J Toxicol Environ Health A. 2000 Feb 25;59(4):229–234. doi: 10.1080/009841000156907. [DOI] [PubMed] [Google Scholar]
  33. Davis K. L., Yesavage J. A., Berger P. A. Single case study. Possible organophosphate-induced parkinsonism. J Nerv Ment Dis. 1978 Mar;166(3):222–225. doi: 10.1097/00005053-197803000-00010. [DOI] [PubMed] [Google Scholar]
  34. Dawson V. L., Brahmbhatt H. P., Mong J. A., Dawson T. M. Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures. Neuropharmacology. 1994 Nov;33(11):1425–1430. doi: 10.1016/0028-3908(94)90045-0. [DOI] [PubMed] [Google Scholar]
  35. Di Monte D., Lawler C. P. Mechanisms of parkinsonism: session X summary and research needs. Neurotoxicology. 2001 Dec;22(6):853–854. doi: 10.1016/s0161-813x(01)00086-9. [DOI] [PubMed] [Google Scholar]
  36. Diedrich J., Wietgrefe S., Zupancic M., Staskus K., Retzel E., Haase A. T., Race R. The molecular pathogenesis of astrogliosis in scrapie and Alzheimer's disease. Microb Pathog. 1987 Jun;2(6):435–442. doi: 10.1016/0882-4010(87)90050-7. [DOI] [PubMed] [Google Scholar]
  37. Dobbs R. J., Charlett A., Dobbs S. M., Weller C., Peterson D. W. Parkinsonism: differential age-trend in Helicobacter pylori antibody. Aliment Pharmacol Ther. 2000 Sep;14(9):1199–1205. doi: 10.1046/j.1365-2036.2000.00815.x. [DOI] [PubMed] [Google Scholar]
  38. Doder M., Jahanshahi M., Turjanski N., Moseley I. F., Lees A. J. Parkinson's syndrome after closed head injury: a single case report. J Neurol Neurosurg Psychiatry. 1999 Mar;66(3):380–385. doi: 10.1136/jnnp.66.3.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Downen M., Amaral T. D., Hua L. L., Zhao M. L., Lee S. C. Neuronal death in cytokine-activated primary human brain cell culture: role of tumor necrosis factor-alpha. Glia. 1999 Nov;28(2):114–127. [PubMed] [Google Scholar]
  40. Duvoisin R. C., Yahr M. D. Epidemiological approach to Parkinson's disease. Lancet. 1972 Jun 24;1(7765):1400–1401. doi: 10.1016/s0140-6736(72)91141-5. [DOI] [PubMed] [Google Scholar]
  41. Earley F. G., Ragan C. I. Photoaffinity labelling of mitochondrial NADH dehydrogenase with arylazidoamorphigenin, an analogue of rotenone. Biochem J. 1984 Dec 1;224(2):525–534. doi: 10.1042/bj2240525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Elizan T. S., Casals J. Astrogliosis in von Economo's and postencephalitic Parkinson's diseases supports probable viral etiology. J Neurol Sci. 1991 Oct;105(2):131–134. doi: 10.1016/0022-510x(91)90135-t. [DOI] [PubMed] [Google Scholar]
  43. Engel L. S., Checkoway H., Keifer M. C., Seixas N. S., Longstreth W. T., Jr, Scott K. C., Hudnell K., Anger W. K., Camicioli R. Parkinsonism and occupational exposure to pesticides. Occup Environ Med. 2001 Sep;58(9):582–589. doi: 10.1136/oem.58.9.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Factor S. A., Sanchez-Ramos J., Weiner W. J. Trauma as an etiology of parkinsonism: a historical review of the concept. Mov Disord. 1988;3(1):30–36. doi: 10.1002/mds.870030105. [DOI] [PubMed] [Google Scholar]
  45. Ferrante R. J., Schulz J. B., Kowall N. W., Beal M. F. Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra. Brain Res. 1997 Apr 4;753(1):157–162. doi: 10.1016/s0006-8993(97)00008-5. [DOI] [PubMed] [Google Scholar]
  46. Ferraz H. B., Bertolucci P. H., Pereira J. S., Lima J. G., Andrade L. A. Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication. Neurology. 1988 Apr;38(4):550–553. doi: 10.1212/wnl.38.4.550. [DOI] [PubMed] [Google Scholar]
  47. Fitsanakis Vanessa A., Amarnath Venkataraman, Moore Joshua T., Montine Kathleen S., Zhang Jing, Montine Thomas J. Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides. Free Radic Biol Med. 2002 Dec 15;33(12):1714–1723. doi: 10.1016/s0891-5849(02)01169-3. [DOI] [PubMed] [Google Scholar]
  48. Fleming L., Mann J. B., Bean J., Briggle T., Sanchez-Ramos J. R. Parkinson's disease and brain levels of organochlorine pesticides. Ann Neurol. 1994 Jul;36(1):100–103. doi: 10.1002/ana.410360119. [DOI] [PubMed] [Google Scholar]
  49. Fontana A., Kristensen F., Dubs R., Gemsa D., Weber E. Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol. 1982 Dec;129(6):2413–2419. [PubMed] [Google Scholar]
  50. Friedman J. H. Progressive parkinsonism in boxers. South Med J. 1989 May;82(5):543–546. doi: 10.1097/00007611-198905000-00002. [DOI] [PubMed] [Google Scholar]
  51. Friedman W. J., Lärkfors L., Ayer-LeLievre C., Ebendal T., Olson L., Persson H. Regulation of beta-nerve growth factor expression by inflammatory mediators in hippocampal cultures. J Neurosci Res. 1990 Nov;27(3):374–382. doi: 10.1002/jnr.490270316. [DOI] [PubMed] [Google Scholar]
  52. Fukushima T., Tawara T., Isobe A., Hojo N., Shiwaku K., Yamane Y. Radical formation site of cerebral complex I and Parkinson's disease. J Neurosci Res. 1995 Oct 15;42(3):385–390. doi: 10.1002/jnr.490420313. [DOI] [PubMed] [Google Scholar]
  53. Gao Hui-Ming, Hong Jau-Shyong, Zhang Wanqin, Liu Bin. Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci. 2002 Feb 1;22(3):782–790. doi: 10.1523/JNEUROSCI.22-03-00782.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Gao Hui-Ming, Jiang Janwei, Wilson Belinda, Zhang Wanqin, Hong Jau-Shyong, Liu Bin. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J Neurochem. 2002 Jun;81(6):1285–1297. doi: 10.1046/j.1471-4159.2002.00928.x. [DOI] [PubMed] [Google Scholar]
  55. Gayle Dave A., Ling ZaoDung, Tong ChongWai, Landers Teresa, Lipton Jack W., Carvey Paul M. Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-alpha, interleukin-1beta, and nitric oxide. Brain Res Dev Brain Res. 2002 Jan 31;133(1):27–35. doi: 10.1016/s0165-3806(01)00315-7. [DOI] [PubMed] [Google Scholar]
  56. Geiger L. E. Etiologies of Parkinsonism. Bull Los Angeles Neurol Soc. 1975 Oct;40(4):160–164. [PubMed] [Google Scholar]
  57. Ghaemi M., Rudolf J., Schmülling S., Bamborschke S., Heiss W. D. FDG- and Dopa-PET in postencephalitic parkinsonism. J Neural Transm (Vienna) 2000;107(11):1289–1295. doi: 10.1007/s007020070018. [DOI] [PubMed] [Google Scholar]
  58. Giulian D., Baker T. J. Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci. 1986 Aug;6(8):2163–2178. doi: 10.1523/JNEUROSCI.06-08-02163.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Giulian D., Baker T. J., Shih L. C., Lachman L. B. Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med. 1986 Aug 1;164(2):594–604. doi: 10.1084/jem.164.2.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Giulian D., Ingeman J. E. Colony-stimulating factors as promoters of ameboid microglia. J Neurosci. 1988 Dec;8(12):4707–4717. doi: 10.1523/JNEUROSCI.08-12-04707.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Giulian D., Johnson B., Krebs J. F., George J. K., Tapscott M. Microglial mitogens are produced in the developing and injured mammalian brain. J Cell Biol. 1991 Jan;112(2):323–333. doi: 10.1083/jcb.112.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Goetz C. G., Pappert E. J. Trauma and movement disorders. Neurol Clin. 1992 Nov;10(4):907–919. [PubMed] [Google Scholar]
  63. Gorell J. M., Johnson C. C., Rybicki B. A., Peterson E. L., Richardson R. J. The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living. Neurology. 1998 May;50(5):1346–1350. doi: 10.1212/wnl.50.5.1346. [DOI] [PubMed] [Google Scholar]
  64. Graeber M. B., Streit W. J., Kreutzberg G. W. Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells. J Neurosci Res. 1988 Sep;21(1):18–24. doi: 10.1002/jnr.490210104. [DOI] [PubMed] [Google Scholar]
  65. Greenamyre J. T., MacKenzie G., Peng T. I., Stephans S. E. Mitochondrial dysfunction in Parkinson's disease. Biochem Soc Symp. 1999;66:85–97. doi: 10.1042/bss0660085. [DOI] [PubMed] [Google Scholar]
  66. Guterman A., Smith R. W. Neurological sequelae of boxing. Sports Med. 1987 May-Jun;4(3):194–210. doi: 10.2165/00007256-198704030-00004. [DOI] [PubMed] [Google Scholar]
  67. Gwinn-Hardy Katrina. Genetics of parkinsonism. Mov Disord. 2002 Jul;17(4):645–656. doi: 10.1002/mds.10173. [DOI] [PubMed] [Google Scholar]
  68. Hansson E., Rönnbäck L. Astrocytes in glutamate neurotransmission. FASEB J. 1995 Mar;9(5):343–350. doi: 10.1096/fasebj.9.5.7534736. [DOI] [PubMed] [Google Scholar]
  69. Heikkila R. E., Nicklas W. J., Vyas I., Duvoisin R. C. Dopaminergic toxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats: implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Neurosci Lett. 1985 Dec 18;62(3):389–394. doi: 10.1016/0304-3940(85)90580-4. [DOI] [PubMed] [Google Scholar]
  70. Heinz G. H., Hill E. F., Contrera J. F. Dopamine and norepinephrine depletion in ring doves fed DDE, dieldrin, and Aroclor 1254. Toxicol Appl Pharmacol. 1980 Mar 30;53(1):75–82. doi: 10.1016/0041-008x(80)90383-x. [DOI] [PubMed] [Google Scholar]
  71. Herishanu Y. O., Medvedovski M., Goldsmith J. R., Kordysh E. A case-control study of Parkinson's disease in urban population of southern Israel. Can J Neurol Sci. 2001 May;28(2):144–147. doi: 10.1017/s0317167100052835. [DOI] [PubMed] [Google Scholar]
  72. Hetier E., Ayala J., Denèfle P., Bousseau A., Rouget P., Mallat M., Prochiantz A. Brain macrophages synthesize interleukin-1 and interleukin-1 mRNAs in vitro. J Neurosci Res. 1988 Oct-Dec;21(2-4):391–397. doi: 10.1002/jnr.490210230. [DOI] [PubMed] [Google Scholar]
  73. Holdorff Bernd. Friedrich Heinrich Lewy (1885-1950) and his work. J Hist Neurosci. 2002 Mar;11(1):19–28. doi: 10.1076/jhin.11.1.19.9106. [DOI] [PubMed] [Google Scholar]
  74. Hornykiewicz O. L-DOPA: from a biologically inactive amino acid to a successful therapeutic agent. Amino Acids. 2002;23(1-3):65–70. doi: 10.1007/s00726-001-0111-9. [DOI] [PubMed] [Google Scholar]
  75. Hu S., Peterson P. K., Chao C. C. Cytokine-mediated neuronal apoptosis. Neurochem Int. 1997 Apr-May;30(4-5):427–431. doi: 10.1016/s0197-0186(96)00078-2. [DOI] [PubMed] [Google Scholar]
  76. Hubble J. P., Cao T., Hassanein R. E., Neuberger J. S., Koller W. C. Risk factors for Parkinson's disease. Neurology. 1993 Sep;43(9):1693–1697. doi: 10.1212/wnl.43.9.1693. [DOI] [PubMed] [Google Scholar]
  77. Hubble J. P., Cao T., Kjelstrom J. A., Koller W. C., Beaman B. L. Nocardia species as an etiologic agent in Parkinson's disease: serological testing in a case-control study. J Clin Microbiol. 1995 Oct;33(10):2768–2769. doi: 10.1128/jcm.33.10.2768-2769.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Hunot S., Boissière F., Faucheux B., Brugg B., Mouatt-Prigent A., Agid Y., Hirsch E. C. Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience. 1996 May;72(2):355–363. doi: 10.1016/0306-4522(95)00578-1. [DOI] [PubMed] [Google Scholar]
  79. Hunot S., Dugas N., Faucheux B., Hartmann A., Tardieu M., Debré P., Agid Y., Dugas B., Hirsch E. C. FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci. 1999 May 1;19(9):3440–3447. doi: 10.1523/JNEUROSCI.19-09-03440.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Höglinger Günter U., Féger Jean, Prigent Annick, Michel Patrick P., Parain Karine, Champy Pierre, Ruberg Merle, Oertel Wolfgang H., Hirsch Etienne C. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem. 2003 Feb;84(3):491–502. doi: 10.1046/j.1471-4159.2003.01533.x. [DOI] [PubMed] [Google Scholar]
  81. Iravani M. M., Kashefi K., Mander P., Rose S., Jenner P. Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration. Neuroscience. 2002;110(1):49–58. doi: 10.1016/s0306-4522(01)00562-0. [DOI] [PubMed] [Google Scholar]
  82. Jellinger K. A. The pathology of Parkinson's disease. Adv Neurol. 2001;86:55–72. [PubMed] [Google Scholar]
  83. Jenner P., Olanow C. W. Understanding cell death in Parkinson's disease. Ann Neurol. 1998 Sep;44(3 Suppl 1):S72–S84. doi: 10.1002/ana.410440712. [DOI] [PubMed] [Google Scholar]
  84. Jeohn G. H., Kim W. G., Hong J. S. Time dependency of the action of nitric oxide in lipopolysaccharide-interferon-gamma-induced neuronal cell death in murine primary neuron-glia co-cultures. Brain Res. 2000 Oct 13;880(1-2):173–177. doi: 10.1016/s0006-8993(00)02737-2. [DOI] [PubMed] [Google Scholar]
  85. Jeohn G. H., Kong L. Y., Wilson B., Hudson P., Hong J. S. Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures. J Neuroimmunol. 1998 May 1;85(1):1–10. doi: 10.1016/s0165-5728(97)00204-x. [DOI] [PubMed] [Google Scholar]
  86. Karen D. J., Li W., Harp P. R., Gillette J. S., Bloomquist J. R. Striatal dopaminergic pathways as a target for the insecticides permethrin and chlorpyrifos. Neurotoxicology. 2001 Dec;22(6):811–817. doi: 10.1016/s0161-813x(01)00063-8. [DOI] [PubMed] [Google Scholar]
  87. Katzenschlager Regina, Lees Andrew J. Treatment of Parkinson's disease: levodopa as the first choice. J Neurol. 2002 Sep;249 (Suppl 2):II19–II24. doi: 10.1007/s00415-002-1204-4. [DOI] [PubMed] [Google Scholar]
  88. Kim Eun Joo, Kwon Kyoung Ja, Park Jee-Young, Lee Soo Hwan, Moon Chang-Hyun, Baik Eun Joo. Neuroprotective effects of prostaglandin E2 or cAMP against microglial and neuronal free radical mediated toxicity associated with inflammation. J Neurosci Res. 2002 Oct 1;70(1):97–107. doi: 10.1002/jnr.10373. [DOI] [PubMed] [Google Scholar]
  89. Kim W. G., Mohney R. P., Wilson B., Jeohn G. H., Liu B., Hong J. S. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci. 2000 Aug 15;20(16):6309–6316. doi: 10.1523/JNEUROSCI.20-16-06309.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Kitazawa M., Anantharam V., Kanthasamy A. G. Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells. Free Radic Biol Med. 2001 Dec 1;31(11):1473–1485. doi: 10.1016/s0891-5849(01)00726-2. [DOI] [PubMed] [Google Scholar]
  91. Klegeris Andis, McGeer Patrick L. Cyclooxygenase and 5-lipoxygenase inhibitors protect against mononuclear phagocyte neurotoxicity. Neurobiol Aging. 2002 Sep-Oct;23(5):787–794. doi: 10.1016/s0197-4580(02)00021-0. [DOI] [PubMed] [Google Scholar]
  92. Kohbata S., Beaman B. L. L-dopa-responsive movement disorder caused by Nocardia asteroides localized in the brains of mice. Infect Immun. 1991 Jan;59(1):181–191. doi: 10.1128/iai.59.1.181-191.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Kohbata S., Shimokawa K. Circulating antibody to Nocardia in the serum of patients with Parkinson's disease. Adv Neurol. 1993;60:355–357. [PubMed] [Google Scholar]
  94. Kostrzewa R. M., Kostrzewa J. P., Brus R. Neuroprotective and neurotoxic roles of levodopa (L-DOPA) in neurodegenerative disorders relating to Parkinson's disease. Amino Acids. 2002;23(1-3):57–63. doi: 10.1007/s00726-001-0110-x. [DOI] [PubMed] [Google Scholar]
  95. Kreutzberg G. W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996 Aug;19(8):312–318. doi: 10.1016/0166-2236(96)10049-7. [DOI] [PubMed] [Google Scholar]
  96. Krüger R., Hardt C., Tschentscher F., Jäckel S., Kuhn W., Müller T., Werner J., Woitalla D., Berg D., Kühnl N. Genetic analysis of immunomodulating factors in sporadic Parkinson's disease. J Neural Transm (Vienna) 2000;107(5):553–562. doi: 10.1007/s007020070078. [DOI] [PubMed] [Google Scholar]
  97. Ladenheim B., Krasnova I. N., Deng X., Oyler J. M., Polettini A., Moran T. H., Huestis M. A., Cadet J. L. Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6. Mol Pharmacol. 2000 Dec;58(6):1247–1256. doi: 10.1124/mol.58.6.1247. [DOI] [PubMed] [Google Scholar]
  98. Langston J. W., Ballard P., Tetrud J. W., Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983 Feb 25;219(4587):979–980. doi: 10.1126/science.6823561. [DOI] [PubMed] [Google Scholar]
  99. Langston J. William. Parkinson's disease: current and future challenges. Neurotoxicology. 2002 Oct;23(4-5):443–450. doi: 10.1016/s0161-813x(02)00098-0. [DOI] [PubMed] [Google Scholar]
  100. Lawson L. J., Perry V. H., Dri P., Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990;39(1):151–170. doi: 10.1016/0306-4522(90)90229-w. [DOI] [PubMed] [Google Scholar]
  101. Lee He-Jin, Shin Soon Young, Choi Chan, Lee Young Han, Lee Seung-Jae. Formation and removal of alpha-synuclein aggregates in cells exposed to mitochondrial inhibitors. J Biol Chem. 2001 Nov 27;277(7):5411–5417. doi: 10.1074/jbc.M105326200. [DOI] [PubMed] [Google Scholar]
  102. Lee S. C., Liu W., Dickson D. W., Brosnan C. F., Berman J. W. Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J Immunol. 1993 Apr 1;150(7):2659–2667. [PubMed] [Google Scholar]
  103. Lewin R. Parkinson's disease: an environmental cause? Science. 1985 Jul 19;229(4710):257–258. doi: 10.1126/science.3925554. [DOI] [PubMed] [Google Scholar]
  104. Lindsay R. M., Wiegand S. J., Altar C. A., DiStefano P. S. Neurotrophic factors: from molecule to man. Trends Neurosci. 1994 May;17(5):182–190. doi: 10.1016/0166-2236(94)90099-x. [DOI] [PubMed] [Google Scholar]
  105. Ling ZaoDung, Gayle Dave A., Ma Shang Yong, Lipton Jack W., Tong Chong Wai, Hong Jau-Shyong, Carvey Paul M. In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain. Mov Disord. 2002 Jan;17(1):116–124. doi: 10.1002/mds.10078. [DOI] [PubMed] [Google Scholar]
  106. Liou H. H., Chen R. C., Tsai Y. F., Chen W. P., Chang Y. C., Tsai M. C. Effects of paraquat on the substantia nigra of the wistar rats: neurochemical, histological, and behavioral studies. Toxicol Appl Pharmacol. 1996 Mar;137(1):34–41. doi: 10.1006/taap.1996.0054. [DOI] [PubMed] [Google Scholar]
  107. Liou H. H., Tsai M. C., Chen C. J., Jeng J. S., Chang Y. C., Chen S. Y., Chen R. C. Environmental risk factors and Parkinson's disease: a case-control study in Taiwan. Neurology. 1997 Jun;48(6):1583–1588. doi: 10.1212/wnl.48.6.1583. [DOI] [PubMed] [Google Scholar]
  108. Liu B., Du L., Hong J. S. Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther. 2000 May;293(2):607–617. [PubMed] [Google Scholar]
  109. Liu B., Jiang J. W., Wilson B. C., Du L., Yang S. N., Wang J. Y., Wu G. C., Cao X. D., Hong J. S. Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther. 2000 Oct;295(1):125–132. [PubMed] [Google Scholar]
  110. Liu Bin, Gao Hui-Ming, Wang Jiz-Yuh, Jeohn Gwang-Ho, Cooper Cynthia L., Hong Jau-Shyong. Role of nitric oxide in inflammation-mediated neurodegeneration. Ann N Y Acad Sci. 2002 May;962:318–331. doi: 10.1111/j.1749-6632.2002.tb04077.x. [DOI] [PubMed] [Google Scholar]
  111. Liu Bin, Hong Jau-Shyong. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther. 2003 Jan;304(1):1–7. doi: 10.1124/jpet.102.035048. [DOI] [PubMed] [Google Scholar]
  112. Louis E. D., Lynch T., Ford B., Greene P., Bressman S. B., Fahn S. Delayed-onset cerebellar syndrome. Arch Neurol. 1996 May;53(5):450–454. doi: 10.1001/archneur.1996.00550050080027. [DOI] [PubMed] [Google Scholar]
  113. Lu X., Bing G., Hagg T. Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience. 2000;97(2):285–291. doi: 10.1016/s0306-4522(00)00033-6. [DOI] [PubMed] [Google Scholar]
  114. Ma Xiaoling C., Gottschall Paul E., Chen Li T., Wiranowska Marzenna, Phelps Christopher P. Role and mechanisms of interleukin-1 in the modulation of neurotoxicity. Neuroimmunomodulation. 2002;10(4):199–207. doi: 10.1159/000068322. [DOI] [PubMed] [Google Scholar]
  115. Marey-Semper I., Gelman M., Lévi-Strauss M. The high sensitivity to rotenone of striatal dopamine uptake suggests the existence of a constitutive metabolic deficiency in dopaminergic neurons from the substantia nigra. Eur J Neurosci. 1993 Aug 1;5(8):1029–1034. doi: 10.1111/j.1460-9568.1993.tb00955.x. [DOI] [PubMed] [Google Scholar]
  116. Mariussen E., Andersson P. L., Tysklind M., Fonnum F. Effect of polychlorinated biphenyls on the uptake of dopamine into rat brain synaptic vesicles: a structure-activity study. Toxicol Appl Pharmacol. 2001 Sep 1;175(2):176–183. doi: 10.1006/taap.2001.9231. [DOI] [PubMed] [Google Scholar]
  117. Maurizi C. P. Influenza and mania: a possible connection with the locus ceruleus. South Med J. 1985 Feb;78(2):207–209. doi: 10.1097/00007611-198502000-00025. [DOI] [PubMed] [Google Scholar]
  118. McCann S. J., LeCouteur D. G., Green A. C., Brayne C., Johnson A. G., Chan D., McManus M. E., Pond S. M. The epidemiology of Parkinson's disease in an Australian population. Neuroepidemiology. 1998;17(6):310–317. doi: 10.1159/000026185. [DOI] [PubMed] [Google Scholar]
  119. McCormack Alison L., Thiruchelvam Mona, Manning-Bog Amy B., Thiffault Christine, Langston J. William, Cory-Slechta Deborah A., Di Monte Donato A. Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis. 2002 Jul;10(2):119–127. doi: 10.1006/nbdi.2002.0507. [DOI] [PubMed] [Google Scholar]
  120. McGeer P. L., Itagaki S., Boyes B. E., McGeer E. G. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology. 1988 Aug;38(8):1285–1291. doi: 10.1212/wnl.38.8.1285. [DOI] [PubMed] [Google Scholar]
  121. McGeer P. L., Yasojima K., McGeer E. G. Inflammation in Parkinson's disease. Adv Neurol. 2001;86:83–89. [PubMed] [Google Scholar]
  122. McGuire S. O., Ling Z. D., Lipton J. W., Sortwell C. E., Collier T. J., Carvey P. M. Tumor necrosis factor alpha is toxic to embryonic mesencephalic dopamine neurons. Exp Neurol. 2001 Jun;169(2):219–230. doi: 10.1006/exnr.2001.7688. [DOI] [PubMed] [Google Scholar]
  123. Meco G., Bonifati V., Vanacore N., Fabrizio E. Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Scand J Work Environ Health. 1994 Aug;20(4):301–305. doi: 10.5271/sjweh.1394. [DOI] [PubMed] [Google Scholar]
  124. Milligan C. E., Cunningham T. J., Levitt P. Differential immunochemical markers reveal the normal distribution of brain macrophages and microglia in the developing rat brain. J Comp Neurol. 1991 Dec 1;314(1):125–135. doi: 10.1002/cne.903140112. [DOI] [PubMed] [Google Scholar]
  125. Minghetti L., Levi G. Induction of prostanoid biosynthesis by bacterial lipopolysaccharide and isoproterenol in rat microglial cultures. J Neurochem. 1995 Dec;65(6):2690–2698. doi: 10.1046/j.1471-4159.1995.65062690.x. [DOI] [PubMed] [Google Scholar]
  126. Miyasaki J. M., Martin W., Suchowersky O., Weiner W. J., Lang A. E. Practice parameter: initiation of treatment for Parkinson's disease: an evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2002 Jan 8;58(1):11–17. doi: 10.1212/wnl.58.1.11. [DOI] [PubMed] [Google Scholar]
  127. Mizuno Y., Hattori N., Kitada T., Matsumine H., Mori H., Shimura H., Kubo S., Kobayashi H., Asakawa S., Minoshima S. Familial Parkinson's disease. Alpha-synuclein and parkin. Adv Neurol. 2001;86:13–21. [PubMed] [Google Scholar]
  128. Mogi M., Harada M., Kondo T., Riederer P., Inagaki H., Minami M., Nagatsu T. Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett. 1994 Oct 24;180(2):147–150. doi: 10.1016/0304-3940(94)90508-8. [DOI] [PubMed] [Google Scholar]
  129. Mogi M., Harada M., Narabayashi H., Inagaki H., Minami M., Nagatsu T. Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease. Neurosci Lett. 1996 Jun 14;211(1):13–16. doi: 10.1016/0304-3940(96)12706-3. [DOI] [PubMed] [Google Scholar]
  130. Mogi M., Harada M., Riederer P., Narabayashi H., Fujita K., Nagatsu T. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994 Jan 3;165(1-2):208–210. doi: 10.1016/0304-3940(94)90746-3. [DOI] [PubMed] [Google Scholar]
  131. Mulhearn R. J. The history of James Parkinson and his disease. Aust N Z J Med. 1971 May;1(Suppl):1–6. doi: 10.1111/j.1445-5994.1971.tb02558.x. [DOI] [PubMed] [Google Scholar]
  132. Müller-Vahl K. R., Kolbe H., Dengler R. Transient severe parkinsonism after acute organophosphate poisoning. J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):253–254. doi: 10.1136/jnnp.66.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  133. Müller T., Blum-Degen D., Przuntek H., Kuhn W. Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson's disease. Acta Neurol Scand. 1998 Aug;98(2):142–144. doi: 10.1111/j.1600-0404.1998.tb01736.x. [DOI] [PubMed] [Google Scholar]
  134. Müller Thomas. Dopaminergic substitution in Parkinson's disease. Expert Opin Pharmacother. 2002 Oct;3(10):1393–1403. doi: 10.1517/14656566.3.10.1393. [DOI] [PubMed] [Google Scholar]
  135. Nayernouri T. Posttraumatic parkinsonism. Surg Neurol. 1985 Sep;24(3):263–264. doi: 10.1016/0090-3019(85)90035-7. [DOI] [PubMed] [Google Scholar]
  136. Neumann H. Control of glial immune function by neurons. Glia. 2001 Nov;36(2):191–199. doi: 10.1002/glia.1108. [DOI] [PubMed] [Google Scholar]
  137. Nishimura M., Mizuta I., Mizuta E., Yamasaki S., Ohta M., Kaji R., Kuno S. Tumor necrosis factor gene polymorphisms in patients with sporadic Parkinson's disease. Neurosci Lett. 2001 Sep 21;311(1):1–4. doi: 10.1016/s0304-3940(01)02111-5. [DOI] [PubMed] [Google Scholar]
  138. Nishimura M., Mizuta I., Mizuta E., Yamasaki S., Ohta M., Kuno S. Influence of interleukin-1beta gene polymorphisms on age-at-onset of sporadic Parkinson's disease. Neurosci Lett. 2000 Apr 21;284(1-2):73–76. doi: 10.1016/s0304-3940(00)00991-5. [DOI] [PubMed] [Google Scholar]
  139. Oehmichen W., Genćić M. Experimental studies on kinetics and functions of monuclear phagozytes of the central nervous system. Acta Neuropathol Suppl. 1975;Suppl 6:285–290. doi: 10.1007/978-3-662-08456-4_50. [DOI] [PubMed] [Google Scholar]
  140. Ogata A., Tashiro K., Nukuzuma S., Nagashima K., Hall W. W. A rat model of Parkinson's disease induced by Japanese encephalitis virus. J Neurovirol. 1997 Apr;3(2):141–147. doi: 10.3109/13550289709015803. [DOI] [PubMed] [Google Scholar]
  141. Olanow C. W., Tatton W. G. Etiology and pathogenesis of Parkinson's disease. Annu Rev Neurosci. 1999;22:123–144. doi: 10.1146/annurev.neuro.22.1.123. [DOI] [PubMed] [Google Scholar]
  142. Petrovitch Helen, Ross G. Webster, Abbott Robert D., Sanderson Wayne T., Sharp Dan S., Tanner Caroline M., Masaki Kamal H., Blanchette Patricia L., Popper Jordan S., Foley Daniel. Plantation work and risk of Parkinson disease in a population-based longitudinal study. Arch Neurol. 2002 Nov;59(11):1787–1792. doi: 10.1001/archneur.59.11.1787. [DOI] [PubMed] [Google Scholar]
  143. Plassman B. L., Havlik R. J., Steffens D. C., Helms M. J., Newman T. N., Drosdick D., Phillips C., Gau B. A., Welsh-Bohmer K. A., Burke J. R. Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology. 2000 Oct 24;55(8):1158–1166. doi: 10.1212/wnl.55.8.1158. [DOI] [PubMed] [Google Scholar]
  144. Pradhan S., Pandey N., Shashank S., Gupta R. K., Mathur A. Parkinsonism due to predominant involvement of substantia nigra in Japanese encephalitis. Neurology. 1999 Nov 10;53(8):1781–1786. doi: 10.1212/wnl.53.8.1781. [DOI] [PubMed] [Google Scholar]
  145. Qin Liya, Liu Yuxin, Cooper Cynthia, Liu Bin, Wilson Belinda, Hong Jau-Shyong. Microglia enhance beta-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species. J Neurochem. 2002 Nov;83(4):973–983. doi: 10.1046/j.1471-4159.2002.01210.x. [DOI] [PubMed] [Google Scholar]
  146. Raivich G., Bohatschek M., Kloss C. U., Werner A., Jones L. L., Kreutzberg G. W. Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Res Brain Res Rev. 1999 Jul;30(1):77–105. doi: 10.1016/s0165-0173(99)00007-7. [DOI] [PubMed] [Google Scholar]
  147. Rajput A. H., Uitti R. J., Stern W., Laverty W., O'Donnell K., O'Donnell D., Yuen W. K., Dua A. Geography, drinking water chemistry, pesticides and herbicides and the etiology of Parkinson's disease. Can J Neurol Sci. 1987 Aug;14(3 Suppl):414–418. doi: 10.1017/s0317167100037823. [DOI] [PubMed] [Google Scholar]
  148. Rao Goutham, Fisch Laura, Srinivasan Sukanya, D'Amico Frank, Okada Tadao, Eaton Carolyn, Robbins Craig. Does this patient have Parkinson disease? JAMA. 2003 Jan 15;289(3):347–353. doi: 10.1001/jama.289.3.347. [DOI] [PubMed] [Google Scholar]
  149. Ritz B., Yu F. Parkinson's disease mortality and pesticide exposure in California 1984-1994. Int J Epidemiol. 2000 Apr;29(2):323–329. doi: 10.1093/ije/29.2.323. [DOI] [PubMed] [Google Scholar]
  150. Sanchez-Ramos J., Facca A., Basit A., Song S. Toxicity of dieldrin for dopaminergic neurons in mesencephalic cultures. Exp Neurol. 1998 Apr;150(2):263–271. doi: 10.1006/exnr.1997.6770. [DOI] [PubMed] [Google Scholar]
  151. Sawada M., Kondo N., Suzumura A., Marunouchi T. Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res. 1989 Jul 10;491(2):394–397. doi: 10.1016/0006-8993(89)90078-4. [DOI] [PubMed] [Google Scholar]
  152. Schiller F. Fritz Lewy and his bodies. J Hist Neurosci. 2000 Aug;9(2):148–151. doi: 10.1076/0964-704X(200008)9:2;1-Y;FT148. [DOI] [PubMed] [Google Scholar]
  153. Schulte Thorsten, Schöls Ludger, Müller Thomas, Woitalla Dirk, Berger Klaus, Krüger Rejko. Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson's disease. Neurosci Lett. 2002 Jun 21;326(1):70–72. doi: 10.1016/s0304-3940(02)00301-4. [DOI] [PubMed] [Google Scholar]
  154. Schwartz J., Elizan T. S. Search for viral particles and virus-specific products in idiopathic Parkinson disease brain material. Ann Neurol. 1979 Sep;6(3):261–263. doi: 10.1002/ana.410060314. [DOI] [PubMed] [Google Scholar]
  155. Seegal R. F., Bush B., Shain W. Lightly chlorinated ortho-substituted PCB congeners decrease dopamine in nonhuman primate brain and in tissue culture. Toxicol Appl Pharmacol. 1990 Oct;106(1):136–144. doi: 10.1016/0041-008x(90)90113-9. [DOI] [PubMed] [Google Scholar]
  156. Seidler A., Hellenbrand W., Robra B. P., Vieregge P., Nischan P., Joerg J., Oertel W. H., Ulm G., Schneider E. Possible environmental, occupational, and other etiologic factors for Parkinson's disease: a case-control study in Germany. Neurology. 1996 May;46(5):1275–1284. doi: 10.1212/wnl.46.5.1275. [DOI] [PubMed] [Google Scholar]
  157. Semchuk K. M., Love E. J., Lee R. G. Parkinson's disease and exposure to agricultural work and pesticide chemicals. Neurology. 1992 Jul;42(7):1328–1335. doi: 10.1212/wnl.42.7.1328. [DOI] [PubMed] [Google Scholar]
  158. Sethi Kapil D. Clinical aspects of Parkinson disease. Curr Opin Neurol. 2002 Aug;15(4):457–460. doi: 10.1097/00019052-200208000-00009. [DOI] [PubMed] [Google Scholar]
  159. Shain W., Bush B., Seegal R. Neurotoxicity of polychlorinated biphenyls: structure-activity relationship of individual congeners. Toxicol Appl Pharmacol. 1991 Oct;111(1):33–42. doi: 10.1016/0041-008x(91)90131-w. [DOI] [PubMed] [Google Scholar]
  160. Sharma R. P., Winn D. S., Low J. B. Toxic, neurochemical and behavioral effects of dieldrin exposure in mallard ducks. Arch Environ Contam Toxicol. 1976;5(1):43–53. doi: 10.1007/BF02220889. [DOI] [PubMed] [Google Scholar]
  161. Sherer Todd B., Betarbet Ranjita, Kim Jin Ho, Greenamyre J. Timothy. Selective microglial activation in the rat rotenone model of Parkinson's disease. Neurosci Lett. 2003 May 1;341(2):87–90. doi: 10.1016/s0304-3940(03)00172-1. [DOI] [PubMed] [Google Scholar]
  162. Sherer Todd B., Betarbet Ranjita, Stout Amy K., Lund Serena, Baptista Melisa, Panov Alexander V., Cookson Mark R., Greenamyre J. Timothy. An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci. 2002 Aug 15;22(16):7006–7015. doi: 10.1523/JNEUROSCI.22-16-07006.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  163. Sherer Todd B., Kim Jin Ho, Betarbet Ranjita, Greenamyre J. Timothy. Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol. 2003 Jan;179(1):9–16. doi: 10.1006/exnr.2002.8072. [DOI] [PubMed] [Google Scholar]
  164. Shohami E., Gallily R., Mechoulam R., Bass R., Ben-Hur T. Cytokine production in the brain following closed head injury: dexanabinol (HU-211) is a novel TNF-alpha inhibitor and an effective neuroprotectant. J Neuroimmunol. 1997 Feb;72(2):169–177. doi: 10.1016/s0165-5728(96)00181-6. [DOI] [PubMed] [Google Scholar]
  165. Stern M., Dulaney E., Gruber S. B., Golbe L., Bergen M., Hurtig H., Gollomp S., Stolley P. The epidemiology of Parkinson's disease. A case-control study of young-onset and old-onset patients. Arch Neurol. 1991 Sep;48(9):903–907. doi: 10.1001/archneur.1991.00530210029018. [DOI] [PubMed] [Google Scholar]
  166. Streit W. J., Graeber M. B., Kreutzberg G. W. Functional plasticity of microglia: a review. Glia. 1988;1(5):301–307. doi: 10.1002/glia.440010502. [DOI] [PubMed] [Google Scholar]
  167. Streit W. J., Walter S. A., Pennell N. A. Reactive microgliosis. Prog Neurobiol. 1999 Apr;57(6):563–581. doi: 10.1016/s0301-0082(98)00069-0. [DOI] [PubMed] [Google Scholar]
  168. Stypuła G., Kunert-Radek J., Stepień H., Zylińska K., Pawlikowski M. Evaluation of interleukins, ACTH, cortisol and prolactin concentrations in the blood of patients with parkinson's disease. Neuroimmunomodulation. 1996 Mar-Jun;3(2-3):131–134. doi: 10.1159/000097237. [DOI] [PubMed] [Google Scholar]
  169. Swerdlow R. H., Parks J. K., Miller S. W., Tuttle J. B., Trimmer P. A., Sheehan J. P., Bennett J. P., Jr, Davis R. E., Parker W. D., Jr Origin and functional consequences of the complex I defect in Parkinson's disease. Ann Neurol. 1996 Oct;40(4):663–671. doi: 10.1002/ana.410400417. [DOI] [PubMed] [Google Scholar]
  170. Tacconi M. T. Neuronal death: is there a role for astrocytes? Neurochem Res. 1998 May;23(5):759–765. doi: 10.1023/a:1022463527474. [DOI] [PubMed] [Google Scholar]
  171. Takahashi H., Wakabayashi K. The cellular pathology of Parkinson's disease. Neuropathology. 2001 Dec;21(4):315–322. doi: 10.1046/j.1440-1789.2001.00403.x. [DOI] [PubMed] [Google Scholar]
  172. Tam S., Barry D. P., Beaman L., Beaman B. L. Neuroinvasive Nocardia asteroides GUH-2 induces apoptosis in the substantia nigra in vivo and dopaminergic cells in vitro. Exp Neurol. 2002 Oct;177(2):453–460. doi: 10.1006/exnr.2002.8012. [DOI] [PubMed] [Google Scholar]
  173. Tanner Caroline M. Is the cause of Parkinson's disease environmental or hereditary? Evidence from twin studies. Adv Neurol. 2003;91:133–142. [PubMed] [Google Scholar]
  174. Taylor C. A., Saint-Hilaire M. H., Cupples L. A., Thomas C. A., Burchard A. E., Feldman R. G., Myers R. H. Environmental, medical, and family history risk factors for Parkinson's disease: a New England-based case control study. Am J Med Genet. 1999 Dec 15;88(6):742–749. [PubMed] [Google Scholar]
  175. Thiffault C., Langston J. W., Di Monte D. A. Increased striatal dopamine turnover following acute administration of rotenone to mice. Brain Res. 2000 Dec 8;885(2):283–288. doi: 10.1016/s0006-8993(00)02960-7. [DOI] [PubMed] [Google Scholar]
  176. Thiruchelvam M., Brockel B. J., Richfield E. K., Baggs R. B., Cory-Slechta D. A. Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson's disease? Brain Res. 2000 Aug 11;873(2):225–234. doi: 10.1016/s0006-8993(00)02496-3. [DOI] [PubMed] [Google Scholar]
  177. Thiruchelvam M., Richfield E. K., Baggs R. B., Tank A. W., Cory-Slechta D. A. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson's disease. J Neurosci. 2000 Dec 15;20(24):9207–9214. doi: 10.1523/JNEUROSCI.20-24-09207.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  178. Thiruchelvam Mona, Richfield Eric K., Goodman Becky M., Baggs Raymond B., Cory-Slechta Deborah A. Developmental exposure to the pesticides paraquat and maneb and the Parkinson's disease phenotype. Neurotoxicology. 2002 Oct;23(4-5):621–633. doi: 10.1016/s0161-813x(02)00092-x. [DOI] [PubMed] [Google Scholar]
  179. Tsai C. H., Lo S. K., See L. C., Chen H. Z., Chen R. S., Weng Y. H., Chang F. C., Lu C. S. Environmental risk factors of young onset Parkinson's disease: a case-control study. Clin Neurol Neurosurg. 2002 Sep;104(4):328–333. doi: 10.1016/s0303-8467(02)00027-6. [DOI] [PubMed] [Google Scholar]
  180. Tüchsen F., Jensen A. A. Agricultural work and the risk of Parkinson's disease in Denmark, 1981-1993. Scand J Work Environ Health. 2000 Aug;26(4):359–362. doi: 10.5271/sjweh.554. [DOI] [PubMed] [Google Scholar]
  181. Unterharnscheidt F. A neurologist's reflections on boxing. V. Conclude remarks. Rev Neurol. 1995 Sep-Oct;23(123):1027–1032. [PubMed] [Google Scholar]
  182. Uversky V. N., Li J., Fink A. L. Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson's disease. FEBS Lett. 2001 Jul 6;500(3):105–108. doi: 10.1016/s0014-5793(01)02597-2. [DOI] [PubMed] [Google Scholar]
  183. Vernadakis A. Neuron-glia interrelations. Int Rev Neurobiol. 1988;30:149–224. [PubMed] [Google Scholar]
  184. Wagner S. R., Greene F. E. Dieldrin-induced alterations in biogenic amine content of rat brain. Toxicol Appl Pharmacol. 1978 Jan;43(1):45–55. doi: 10.1016/s0041-008x(78)80031-3. [DOI] [PubMed] [Google Scholar]
  185. Wetmur J. G., Schwartz J., Elizan T. S. Nucleic acid homology studies of viral nucleic acids in idiopathic Parkinson's disease. Arch Neurol. 1979 Aug;36(8):462–464. doi: 10.1001/archneur.1979.00500440032004. [DOI] [PubMed] [Google Scholar]
  186. Williams D. B., Annegers J. F., Kokmen E., O'Brien P. C., Kurland L. T. Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology. 1991 Oct;41(10):1554–1557. doi: 10.1212/wnl.41.10.1554. [DOI] [PubMed] [Google Scholar]
  187. Wu D. C., Jackson-Lewis Vernice, Vila Miquel, Tieu Kim, Teismann Peter, Vadseth Caryn, Choi Dong-Kug, Ischiropoulos Harry, Przedborski Serge. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002 Mar 1;22(5):1763–1771. doi: 10.1523/JNEUROSCI.22-05-01763.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  188. Xie Zhong, Wei Min, Morgan Todd E., Fabrizio Paola, Han Derick, Finch Caleb E., Longo Valter D. Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and lipopolysaccharide-activated microglia. J Neurosci. 2002 May 1;22(9):3484–3492. doi: 10.1523/JNEUROSCI.22-09-03484.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  189. Yamada T., McGeer P. L., McGeer E. G. Lewy bodies in Parkinson's disease are recognized by antibodies to complement proteins. Acta Neuropathol. 1992;84(1):100–104. doi: 10.1007/BF00427222. [DOI] [PubMed] [Google Scholar]
  190. Yumino Kunio, Kawakami Ikuo, Tamura Mamoru, Hayashi Takaaki, Nakamura Masao. Paraquat- and diquat-induced oxygen radical generation and lipid peroxidation in rat brain microsomes. J Biochem. 2002 Apr;131(4):565–570. doi: 10.1093/oxfordjournals.jbchem.a003135. [DOI] [PubMed] [Google Scholar]
  191. Zhang Jing, Fitsanakis Vanessa A., Gu Guangyu, Jing Deqiang, Ao Mingfang, Amarnath Venkataraman, Montine Thomas J. Manganese ethylene-bis-dithiocarbamate and selective dopaminergic neurodegeneration in rat: a link through mitochondrial dysfunction. J Neurochem. 2003 Jan;84(2):336–346. doi: 10.1046/j.1471-4159.2003.01525.x. [DOI] [PubMed] [Google Scholar]
  192. de Silva H. R., Khan N. L., Wood N. W. The genetics of Parkinson's disease. Curr Opin Genet Dev. 2000 Jun;10(3):292–298. doi: 10.1016/s0959-437x(00)00082-4. [DOI] [PubMed] [Google Scholar]
  193. del Rio-Hortega P. Art and artifice in the science of histology. 1933. Histopathology. 1993 Jun;22(6):515–525. doi: 10.1111/j.1365-2559.1993.tb00171.x. [DOI] [PubMed] [Google Scholar]

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