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2006 Fiscal Year Final Research Report Summary

Study of the autoimmune mechanism in narcolepsy using gene expressional profiling

Research Project

Project/Area Number 17390324
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

HONDA Makoto  Tokyo Metropolitan Organization for Medical Research, Tokyo Institute of Psychiatry, Research Director, 東京都精神医学総合研究所, 副参事研究員 (50370979)

Co-Investigator(Kenkyū-buntansha) TANAKA Susumu  Tokyo Metropolitan Organization for Medical Research, Tokyo Institute of Psychiatry, Post-Doctoral fellow, 東京都精神医学総合研究所, 研究員 (30399472)
KAWASHIMA Minae  The University of Tokyo, Graduate School of Medicine, Department of Sleep Analysis, Staff, 大学院医学系研究科・寄附講座, 教員 (00396706)
HONDA Yutaka  Neuropsychiatric Research Institute, President, 理事長 (90010305)
Project Period (FY) 2005 – 2006
Keywordsgene expressional profiling / narcolepsy / autoantibody
Research Abstract

Narcolepsy is a common sleep disorder characterized by excessive daytime sleepiness, cataplexy (sudden loss of muscle tone triggered by emotion) and other manifestations of abnormal REM sleep. The pathophysiology of narcolepsy involves the HLA and hypocretin neurotransmission. Almost all cases with narcolepsy share a common HLA allele, DQB1^*0602 suggesting an autoimmune basis for the disorder. Over 90% of narcolepsy cases are associated with a dramatic decrease in hypocretin-1 (HCRT1) in the cerebrospinal fluid. Immunohistochemical studies also revealed a more than 90% decrease in HCRT cell count in the hypothalamus of narcoleptic subjects. In this study, we have used postmortem human brain samples to compare the transcriptome of narcoleptic versus control subjects. Our primary goal was to identify other genes that may be dysregulated in the posterior hypothalamus of narcoleptic patients. We have also developed a novel radioligand binding assay system to address the question whether a … More utoantibodies against hypocretin and hypocretin receptors and other identified narcolepsy-related genes were involved in narcolepsy pathophysiology or not.
Out of 11 upregulated and 35 downregulated genes in narcolepsy, 9 downregulated genes were verified with quantitative RT-PCR. Hypocretin was the most downregulated gene. One of these 9 genes, insulin-like growth factor binding protein(IGFBP), was confirmed to be highly expressed in hypocretin neurons. Sera from narcolepsy and control subjects were compared for the presence of autoantibodies against hypocretin, its receptors, and IGFBP. We detected autoantibodies against hypocretin in 3 patients, hcrtr1 in 1 patient, and hcrtr2 in 5 patients, but the finding was not disease specific. We were unable to find autoantibodies against IGFBP. Our results do not support the hypothesis that autoantibody-mediated dysfunction in the hypocretin system underlies the pathophysiology of narcolepsy. However IGFBP is known to have proapoptotic properties and may be involved in the pathogenesis of narcolepsy. Less

  • Research Products

    (6 results)

All 2006 Other

All Journal Article (6 results)

  • [Journal Article] Detection of autoantibodies against hypocretin, hcrtr1, and hcrtr2 in narcolepsy : anti-Hcrt system antibody in narcolepsy2006

    • Author(s)
      Tanaka S, Honda Y, Inoue Y, Honda M
    • Journal Title

      Sleep 29

      Pages: 633-638

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Detection of autoantibodies against hypocretin, hcrtr1, and hcrtr2 in narcolepsy : anti-Hcrt system antibody in narcolepsy.2006

    • Author(s)
      Tanaka S, Honda Y, Inoue Y, Honda M.
    • Journal Title

      Sleep 29

      Pages: 633-638

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of differentially expressed genes in blood cells of narcolepsy patients

    • Author(s)
      Tanaka S, Honda Y, Honda M
    • Journal Title

      Sleep (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ナルコレプシー(居眠り病)の原因遺伝子研究 : 睡眠障害の分子生物学

    • Author(s)
      本多 真
    • Journal Title

      実験医学 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of differentially expressed genes in blood cells of narcolepsy patients

    • Author(s)
      Tanaka S, Honda Y, Honda M.
    • Journal Title

      Sleep (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Study for the cause of narcolepsy gene : molecular biology of sleep disorders

    • Author(s)
      Honda M.
    • Journal Title

      Experimental Medicine (in Japanese) (in press)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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