Isatin, an endogenous MAO inhibitor, and a rat model of Parkinson’s disease induced by the Japanese encephalitis virus

  • M. Minami
  • N. Hamaue
  • M. Hirafuji
  • H. Saito
  • T. Hiroshige
  • A. Ogata
  • K. Tashiro
  • S. H. Parvez
Part of the Journal of Neural Transmission. Supplementa book series (NEURALTRANS, volume 71)


A single dose of isatin (indole-2,3-dione)(i.p.), an endogenous MAO inhibitor, significantly increased norepinephrine and 5-hydroxytryptamine concentrations in the rat brain and also significantly increased acetylcholine and dopamine (DA) levels in the rat striatum. Urinary isatin concentrations in patients with Parkinson’s disease tend to increase according to the severity of disease. We have developed a rat model of Parkinson’s disease induced by the Japanese encephalitis virus (JEV). The distribution of the pathological lesions of JEV-rats resemble those found in Parkinson’s disease. Significant behavioral improvement was observed in JEV-rats after isatin, L-DOPA and selegiline administration using a pole test. Both isatin and selegiline prevented the decrease in striatum DA levels of JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not selegiline. These findings suggest that JEV-infected rats may serve as a model of Parkinson’s disease and that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.


Atrial Natriuretic Peptide Japanese Encephalitis Japanese Encephalitis Virus Striatal Cholinergic Interneuron Postencephalitic Parkinsonism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adams JD, Odunze IN (1991) Oxygen free radicals and Parkinson’s disease. Free Radical Biol Med 10: 161–169CrossRefGoogle Scholar
  2. Alves RSC, Barbosa ER, Scaff M (1992) Postvaccinial parkinsonism. Movement Disorders 7: 178–180PubMedCrossRefGoogle Scholar
  3. Appel SH, Le WD, Tajti J, Haverkamp LJ, Engelhardt JI (1992) Nigral damage and dopaminergic hypofunction in mesencephalon-immunized guinea pigs. Ann Neurol 32: 494–501PubMedCrossRefGoogle Scholar
  4. Armando I, Barontini M, Levin G, Simsolo R, Glover V, Sandler M (1984) Exercise increases endogenous urinary monoamine oxidase benzodiazepine receptor ligand inhibitory activity in normal children. J Auton Nerv Syst 11: 95–100PubMedCrossRefGoogle Scholar
  5. Armando I, Levin G, Barontini M (1988) Stress increases endogenous benzodiazepine receptor ligand-monoamine oxidase inhibitory activity (tribulin) in rat tissues. J Neural Transm 71: 29–37PubMedCrossRefGoogle Scholar
  6. Battacharya SK, Glover V, Sandler M, Clow A, Topham A, Bernadt M, Murray R (1982) Raised endogenous monoamine oxidase inhibitor output in postwithdrawal alcoholics: effects of L-dopa and ethanol. Biol Psychiat 17: 829–836Google Scholar
  7. Battacharya SK, Acharya SB (1993) Further investigations on the anxiogenic effects of isatin. Biog Amines 9: 453–463Google Scholar
  8. Battacharya SK, Chakrabarti A, Sandler M, Glover V (1996) Anxyolytic activity of intraventricularly administered atrial natriuretic peptide in the rat. Neuropsycho-pharmacol 15: 199–206CrossRefGoogle Scholar
  9. Ballard PA, Tetrud JW, Langston JW (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. Neurology 35: 949–956PubMedGoogle Scholar
  10. Bansal RC, Kaur P, Kiran R (1988) Mode of interaction of isatin with rat liver alkaline phosphatase. Res Bull (Science) PU Chandigarh 39: 71–76Google Scholar
  11. Berry MD, Juorio AV, Paterson IA (1994) Possible mechanisms of action of (−)deprenyl and other MAO-B inhibitors in some neurologic and psychiatric disorders. Prog Neurobiol 44: 141–161PubMedCrossRefGoogle Scholar
  12. Blaschko H (1973) Amine oxidase. In: Boyer PD, Lardy H, Myrback K (eds) The Enzymes. 3rd ed, vol 8, Academic Press, New York, pp 337–351Google Scholar
  13. Bojinov S (1971) Encephalitis with acute parkinsonian syndrome and bilateral inflammatory necrosis of the substantia nigra. J Neurol Sci 12: 383–415PubMedCrossRefGoogle Scholar
  14. Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80: 4546–4550PubMedCrossRefGoogle Scholar
  15. Bursey M, Eichenbaum H (1996) Conservation of hippocampal memory function in rats and humans. Nature 379: 255–257CrossRefGoogle Scholar
  16. Calne DB, Langston JW (1983) Aetiology of Parkinson’s disease. Lancet 2: 1457–1459PubMedCrossRefGoogle Scholar
  17. Chocholova L, Kolinova M (1979) Effect of isatin on audiogenic seizures in rats and its relationship to electrographic and behavioral phenomena. Physiol Bohemoslov 28: 495–502PubMedGoogle Scholar
  18. Chocholova L, Kolinova M (1981) Effect of isatin (2, 3 dioxyindoline) on physiological and pathological electrographic manifestations of vigilance. Physiol Bohemoslov 30: 129–137PubMedGoogle Scholar
  19. Clow A, Glover V, Armando I, Sandler M (1983) New endogenous benzodiazepine receptor ligand in human urine: identity with endogenous MAO inhibitor? Life Sci 33: 735–741PubMedCrossRefGoogle Scholar
  20. Clow A, Glover V, Weg MW, Walker PL, Sheehan DV, Carr DB, Sandler M (1988a) Urinary catecholamine metabolite and tribulin output during lactate infusion. Br J Psychiatry 152: 122–126PubMedGoogle Scholar
  21. Clow A, Glover V, Sandler M, Tiller J (1988b) Increased urinary tribulin output in generalized anxiety disorder. Psychopharmacol 95: 378–380Google Scholar
  22. Cohen G (1986) Monoamine oxidase, hydrogen peroxidase and Parkinson’s disease. Adv Neurol 45: 119–125Google Scholar
  23. Dexter DT, Wells FR, Lees AJ, Agid F, Agid Y, Jenner P, Marsden CD (1989) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem 52: 1830–1836PubMedCrossRefGoogle Scholar
  24. Dickerson RB, Newton JR, Hansen JE (1952) Diagnosis and immediate prognosis of Japanese B encephalitis. Am J Med 12: 277–288PubMedCrossRefGoogle Scholar
  25. Duvoisin RC, Yahr MD (1965) Encephalitis and parkinsonism. Arch Neurol 12: 227–239PubMedGoogle Scholar
  26. Elsworth JD, Dewar D, Glover V, Goodwin BL, Clow A, Sandler M (1986) Purification and characterization of tribulin, an endogenous inhibitor of monoamine oxidase and benzodiazepine receptor binding. J Neural Transm 67: 45–56PubMedCrossRefGoogle Scholar
  27. Fishman PS, Gass JS, Swoveland PT, Lavi E, Highkin MK, Weiss SR (1985) Infection of the basal ganglia by a murine coronavirus. Science 229: 877–879PubMedCrossRefGoogle Scholar
  28. Geddes JF, Hughes AJ, Lees AJ, Daniel SE (1993) Pathological overlap in cases of parkinsonism associated with neurofibrillary tangles. A study of recent cases of postencephalitic parkinsonism and comparison with progressive supranuclear palsy and Guamanian parkinsonism-dementia complex. Brain 116: 281–302PubMedGoogle Scholar
  29. Gerlach M, Youdim MB, Riederer P (1996) Pharmacology of selegiline. Neurology 47[Suppl 3]: S137–S145PubMedGoogle Scholar
  30. Gibb WRG, Lees AJ (1987) The progression of idiopathic Parkinson’s disease is not explained by age-related changes. Clinical and pathological comparisons with post-encephalitic parkinsonian syndrome. Acta Neuropathol (Berl) 73: 195–201PubMedCrossRefGoogle Scholar
  31. Glover V, Reveley MA, Sandler M (1980) A monoamine oxidase inhibitor in human urine. Biochem Pharmacol 29: 467–470PubMedCrossRefGoogle Scholar
  32. Glover V, Halket JM, Watkins PJ, Clow A, Goodwin BL, Sandler M (1988) Isatin: identity with the purified endogenous monoamine oxidase inhibitor tribulin. J Neurochem 51: 656–659PubMedCrossRefGoogle Scholar
  33. Glover V, Bhattacharya SK, Sandler M (1991) Isatin-a new biological factor. Indian J Exp Biol 29: 1–5PubMedGoogle Scholar
  34. Glover V, Clow A, Sandler M (1993) Effects of dopaminergic drugs on superoxide dismutase: implications for senescence. J Neurol Transm 40[Suppl]: 37–45Google Scholar
  35. Glover V, Medvedev A, Sandler M (1995) Isatin is a potent endogenous antagonist of guanylate cyclase-coupled atrial natriuretic peptide receptors. Life Sci 57: 2073–2079PubMedCrossRefGoogle Scholar
  36. Gorell JM, Czarnecki B (1986) Pharmacological evidence for direct dopaminergic regulation of striatal acetylcholine release. Life Sci 38: 2239–2246PubMedCrossRefGoogle Scholar
  37. Goto A (1962) Follow-up study of Japanese B encephalitis. Psychiat Neurol Jpn (Tokyo) 64: 236–266Google Scholar
  38. Hamaue N, Minami M, Kanamaru Y, Togashi M, Monma Y, Ishikura M, Mahara R, Yamazaki N, Togashi H, Saito H, Parvez SH (1992) Endogenous monoamine oxidase (MAO) inhibitor (tribulin-like activity) in the brain and urine of stroke-prone SHR. Biog Amines 8: 401–412Google Scholar
  39. Hamaue N, Minami M, Kanamaru Y, Ishikura M, Yamazaki N, Saito H, Parvez SH (1994) Identification of isatin, an endogenous MAO inhibitor, in the brain of stroke-prone SHR. Biog Amines 10: 99–110Google Scholar
  40. Hamaue N, Yamazaki N, Minami M, Endo T, Hirafuji M, Monma Y, Togashi H (1998) Determination of isatin, an endogenous monoamine oxidase inhibitor, in urine and tissues of rats by HPLC. Gen Pharmacol 30: 387–391PubMedCrossRefGoogle Scholar
  41. Hamaue N, Yamazaki N, Minami M, Endo T, Hirafuji M, Monma Y, Togashi H, Saito H, Parvez SH (1999a) Effects of isatin, an endogenous MAO inhibitor, on acetylcholine and dopamine levels in the rat striatum. Biog Amines 15: 367–377Google Scholar
  42. Hamaue N, Minami M, Hirafuji M, Terado M, Machida M, Yamazaki N, Yoshioka M, Ogata A, Tashiro K (1999b) Isatin, an endogenous MAO inhibitor, as a new biological modulator. CNS Drug Rev 5: 331–346CrossRefGoogle Scholar
  43. Hamaue N, Yamazaki N, Terado M, Minami M, Ohno K, Ide H, Ogata A, Honma S, Tashiro K (2000) Urinary isatin concentrations in patients with Parkinson’s disease determined by a newly developed HPLC-UV method. Res Commun Mol Pathol Pharmacol 108: 63–73PubMedGoogle Scholar
  44. Hamaue N, Minami M, Terado M, Hirafuji M, Endo T, Machida M, Hiroshige T, Ogata A, Tashiro K, Saito H, Parvez SH (2004) Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and selegiline on bradykinesia and dopamine levels in a rat model of Parkinson’s disease induced by the Japanese encephalitis virus. NeuroToxicology 25: 205–213PubMedCrossRefGoogle Scholar
  45. Hoehn MM, Yarh MD (1967) Parkinsonism: onset, progression and mortality. Neurolol 17: 427–442Google Scholar
  46. Hota D, Acharya SB (1994) Studies on peripheral actions of isatin. Ind J Exp Biol 32: 710–717Google Scholar
  47. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29: 577–580PubMedGoogle Scholar
  48. Hudson AJ, Rice GPA (1990) Similarities of Guamanian ALS/PD to postencephalitic parkinsonism/ALS: possible viral cause. Can J Neurol Sci 17: 427–433PubMedGoogle Scholar
  49. Imperato A, Obinu MC, Casu A, Mascia S, Dazzi L, Gessa GL (1993) Evidence that neuroleptics increase striatal acetylcholine release though stimulation of dopamine D1 receptors. J Pharmacol Exp Ther 266: 557–562PubMedGoogle Scholar
  50. Jarman J, Przylorowska A, Glover V, Halket J, Davies PT, Rose FC, Sandler M (1991) Urinary output of endogenous monoamine oxidase inhibitor and isatin during acute migraine attack. J Neural Transm Gen Sect 84: 129–134PubMedCrossRefGoogle Scholar
  51. Johnson RT, Burke DS, Elwell M, Leake CJ, Nisalak A, Hoke CH, Lorsomrudee W (1985) Japanese encephalitis: immunocytochemical studies of viral antigen and inflammatory cells in fatal cases. Ann Neurol 18: 567–573PubMedCrossRefGoogle Scholar
  52. Knoll J (1978) The possible mechanisms of action of (−)deprenyl in Parkinson’s disease. J Neural Transm 43: 177–198PubMedCrossRefGoogle Scholar
  53. Kristensson K (1992) Potential role of viruses in neuro-degeneration. Mol Chem Neuropathol 16: 45–58PubMedCrossRefGoogle Scholar
  54. Kumar P, Dani HM, Trehan S (1977) Effect of isatin testicular hyaluronidase. Ind J Exp Biol 15: 655–656Google Scholar
  55. Kumar P, Bansal RC, Mahmood A (1993) Isatin, an inhibitor of acetylcholinesterase activity in rat brain. Biog Amines 9: 281–289Google Scholar
  56. Lehmann J, Langer SZ (1983) The striatal cholinergic interneuron: Synaptic target of dopaminergic terminals? Neurosci 10: 1105–1120CrossRefGoogle Scholar
  57. Matsumoto M, Togashi H, Yoshioka M, Hirokami M, Morii K, Saito H (1990) Simultaneous high-performance liquid chromatographic determination of norepinephrine, serotonin, acetylcholine and their metabolites in the cerebrospinal fluid of anaesthetized normotensive rats. J Chromatogr 526: 1–10PubMedGoogle Scholar
  58. McIntyre IM, Norman TR (1990) Serotonergic effects of isatin: an endogenous MAO inhibitor related to tribulin. J Neural Transm 79: 35–40CrossRefGoogle Scholar
  59. McGeer PL, Itagaki S, Akiyama H, McGeer EG (1988) Rate of cell death in parkinsonism indicates active neuropathological process. Ann Neurol 24: 574–576PubMedCrossRefGoogle Scholar
  60. Medvedev AE, Clow A, Sandler M, Glover V (1996) Isatin: A link between natriuretic peptides and monoamines? Biochem Pharmacol 52: 385–391PubMedCrossRefGoogle Scholar
  61. Minami M, Senjo M, Togashi H, Yoshioka M, Saito H, Kawaguchi H, Takebayashi K, Parvez H (1988) Kidney glutathione S-transferase activity and kidney monoamine oxidase activity in stroke cases of SHRSP. Biog Amines 5: 517–526Google Scholar
  62. Morita K, Tanaka M, Igarashi A (1991) Rapid identification of dengue virus serotypes by using polymerase chain reaction. J Clin Microbiol 29: 2107–2110PubMedGoogle Scholar
  63. Muller M, Schramek J (1989) Combined application of propranolol and local anesthetics: enhanced anticonvulsant action. Biomed Biochim Acta 4: 333–336Google Scholar
  64. Nagatsu T, Yoshida M (1988) An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primate with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions. Neurosci Lett 87: 178–182PubMedCrossRefGoogle Scholar
  65. Nilsson OG, Leanza G, Bjkölund A (1992) Acetylcholine release in the hippocampus: regulation by monoaminergic afferents as assessed by in vivo microdialysis. Brain Res 584: 132–140PubMedCrossRefGoogle Scholar
  66. Ogata A, Nagashima K, Hall WW, Ichikawa M, Kimura-Kuroda J, Yasui K (1991) Japanese encephalitis virus neurotropism is dependent on the degree of neuronal maturity. J Virol 65: 880–886.PubMedGoogle Scholar
  67. Ogata A, Tashiro K, Nukuzuma S, Nagashima K, Hall WW (1997) A rat model of Parkinson’s disease induced by Japanese encephalitis virus. J Neurol Virol 3: 141–147Google Scholar
  68. Ogata A, Nagashima K, Yasui K, Matsuura T, Tashiro K (1998) Sustained release dosage of thyrotropin-releasing hormone improves experimental Japanese encephalitis virus-induced parkinsonism in rats. J Neurol Sci 159: 135–139PubMedCrossRefGoogle Scholar
  69. Ogata A, Hamaue N, Terado M, Minami M, Nagashima K, Tashiro K (2003) Isatin, an endogenous MAO inhibitor, improves bradykinesia and dopamine levels in a rat model of Parkinson’s disease induced by Japanese encephalitis virus. J Neurol Sci 206: 79–83PubMedCrossRefGoogle Scholar
  70. Ogata A, Hamaue N, Minami M, Yabe I, Kikuchi S, Sasaki H, Tashiro K (2004) Post-encephalitis parkinsonism: clinical features and experimental model. Biog Amines 18: 339–347CrossRefGoogle Scholar
  71. Ogawa N, Hirose Y, Ohara S, Ono T, Watanabe Y (1985) A simple quantitative bradykinesia test in MPTP-treated mice. Res Commun Chem Pathol Pharmaco 50: 435–441Google Scholar
  72. Ohue T, Koshimura K, Akiyama Y, Ito A, Kido T, Takagi Y, Miwa S (1992) Regulation of acetylcholine release in vivo from rat hippocampus by monoamines as revealed by novel column-switching HPLC with electrochemical detection. Brain Res 572: 340–344PubMedCrossRefGoogle Scholar
  73. Oxenkrug G, McIntyre I (1985) Stress-induced synthesis of melatonin; possible involvement of the endogenous monoamine oxidase inhibitor (tribulin). Life Sci 37: 1743–1746PubMedCrossRefGoogle Scholar
  74. Parvez H, Parvez S (1973) The effects of metopirone and adrenectomy on the regulation of the enzymes monoamine oxidase and catechol-O-methyl transferase in different brain regions. J Neurochem 20: 1011–1020PubMedCrossRefGoogle Scholar
  75. Paxinos G, Wason C (1980) The rat brain in stereotaxic coordinates. 2nd ed, New York, Academic Press IncGoogle Scholar
  76. Peturson H, Bhattacharya SK, Glover V, Sandler M, Lader MH (1982) Urinary monoamine oxidase inhibitor and benzodiazepine withdrawal. Br J Psychiat 140: 7–10CrossRefGoogle Scholar
  77. Riederer P, Sotic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K, Youdim MB (1989) Transition metals ferritin, glutathione and ascorbic acid in Parkinsonian brain. J Neurochem 52: 515–520PubMedCrossRefGoogle Scholar
  78. Sandler M (1982) The emergence of tribulin. Trends Pharmacol Sci 3: 471–472CrossRefGoogle Scholar
  79. Scatton B (1992) Further evidence for the involvement of D2, but not D1 dopamine receptors in dopaminergic control of striatal cholinergic transmission. Life Sci 31: 2883–2890CrossRefGoogle Scholar
  80. Sethy VH, van Woert MH (1974) Regulation of striatal acetylcholine concentration by dopamine receptors. Nature 251: 529–530PubMedCrossRefGoogle Scholar
  81. Shoji H, Watanabe M, Itoh S, Kuwahara H, Hattori F (1993) Japanese encephalitis and parkinsonism. J Neurol 240: 59–60PubMedCrossRefGoogle Scholar
  82. Singh B, Sharma R, Sareen K, Sareen KN, Sohal MS (1977) Isatin enzyme interaction V. Activation of rat liver acid phosphatase. Enzyme 22: 256–261PubMedGoogle Scholar
  83. Stadler H, Lloyd KG, Gadea-Ciria M, Bartholini G (1973) Enhanced striatal acetylcholine release by chlorpromazine and its reversal by apomorphine. Brain Res 55: 476–480PubMedCrossRefGoogle Scholar
  84. Stoof JC, Drukarch B, DeBoer P, Westerink BHC, Groenewegen HJ (1992) Regulation of the activity of striatal cholinergic neurons by L-DOPA. Neurosci 47: 755–770CrossRefGoogle Scholar
  85. Sumiyoshi H, Mori C, Fuke I, Morita K, Kuhara S, Kondou J, Kikuchi Y, Nagamatu H, Igarashi A (1987) Complete nucleotide sequence of the Japanese encephalitis virus genome RNA. Virology 161: 497–510PubMedCrossRefGoogle Scholar
  86. Susheela I, Singh B, Dani HM, Amma MKP, Sareen K (1969) Enzyme inhibition by isatin I. Inhibition of rat liver xanthine oxidase. Enzymol 37: 325–334Google Scholar
  87. Takahashi M, Yamada T, Nakajima S, Nakajima K, Yamamoto T, Okada H (1995) The substantia nigra is a major target for neurovirulent influenza A virus. J Exp Med 181: 2161–2169PubMedCrossRefGoogle Scholar
  88. Tipton KF, Housy MD, Mantle TJ (1976) The nature and locations of the multiple forms of monoamine oxidase. In: Mary LC (ed) Monoamine oxidase: its inhibition. Elsevier, New York, pp 5–31Google Scholar
  89. Tozawa Y, Ueki A, Manabe S, Matsushima K (1998) Stress-induced increase in urinary isatin excretion in rats: reversal by both dexamethasone and α-methyl-p-tyrosine. Biochem Pharmacol 56: 1041–1046PubMedCrossRefGoogle Scholar
  90. Ueki A, Willoughby J, Glover V, Sandler M, Stibbe K, Stern GM (1989) Endogenous urinary monoamine oxidase inhibitor excretion in Parkinson’s disease and other neurological disorders. J Neural Transm 1: 263–268CrossRefGoogle Scholar
  91. Von Economo C (1917) Encephalitis lethargica. Wien klin Wschr 30: 581–585Google Scholar
  92. Walters JH (1960) Post-encephalitic parkinson syndrome after meningoencephalitis due to coxsackie virus group B, type 2. New Eng J Med 263: 744–747CrossRefGoogle Scholar
  93. Wedzong K, Limberger N, Spath L, Wichman T, Stare K (1988) Acethylcholine release in rat nucleus accumbens is regulated though dopamine D2-receptor. Naunym-Schmied Arch Pharmacol 338: 250–255Google Scholar
  94. Yahr MD (1978) Encephalitis lethargica (Von Economo’s disease, epidemic encephalitis). In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology vol 34 Elsevier, Amsterdam, pp 451–457Google Scholar
  95. Yang HYT, Neff NH (1974) The monoamine oxidases of brain: selective inhibition with drugs and the consequences for the metabolism of the biogenic amines. J Pharmacol Exp Ther 189: 733–740PubMedGoogle Scholar
  96. Yoshida M, Miwa T, Nagatsu T (1990) Parkinsonism in monkeys produced by chronic administration of an endogenous substance of the brain, tetrahy droisoquinoline: the behavioral and biochemical changes. Neurosci Lett 119: 109–113PubMedCrossRefGoogle Scholar
  97. Yumiler A (1990) The effect of isatin (tribulin) on metabolism of indoles in the rat brain and pineal: in vitro and pineal: in vitro and in vivo studies. Neurochem Res 15: 95–100CrossRefGoogle Scholar

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© Springer-Verlag 2006

Authors and Affiliations

  • M. Minami
    • 1
    • 4
    • 5
  • N. Hamaue
    • 1
  • M. Hirafuji
    • 1
  • H. Saito
    • 1
  • T. Hiroshige
    • 1
  • A. Ogata
    • 2
  • K. Tashiro
    • 2
  • S. H. Parvez
    • 3
  1. 1.The Research Institute of Personalized Health ScienceHealth Science University of HokkaidoIshikari-TobetsuJapan
  2. 2.Department of NeurologyHokkaido University Graduate School of MedicineSapporoJapan
  3. 3.Alfred Fressard Institute of NeuroscienceCNRS UPRGif Sur YvetteFrance
  4. 4.Health Science University of HokkaidoJapan
  5. 5.Unit of Geriatrics: OhzoraTouei HospitalSapporoJapan

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