Transcriptional regulation of orexin by candidate genes for narcolepsy

• Project/Area Number: 20790868
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: TANAKA Susumu Tokyo Metropolitan Organization for Medical Research, 東京都精神医学総合研究所, 研究員 (30399472)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ナルコレプシー / ORX / IGFBP3 / NR6A1 / 転写制御 / オレキシン / Nur77 / 睡眠

Research Abstract

In this study, I examined the activities of transcriptional modulations of two narcolepsy candidate genes, IGFBP3 and NR6A1, against ORX transcription. (1)IGFBP3 and NR6A1 expression were found in hypothalamic ORX neurons by immunehistochemical studies. (2)By using reporter assay, IGFBP3 and NR6A1 modulated ORX promoter activity in several cell lines. (3)IGFBP3 overexpression mice showed the reduction of hypothalamic ORX expression and modulated sleep conditions. I also found NR6A1 overexpression modulated ORX expression, however the mice number examined have not reached statistically enough yet.

Research Products

• [Journal Article] IgG Abnormality in Narcolepsy and Idiopathic Hypersomnia. (2010)
  • Author(s): Tanaka S, Honda M
  • Journal Title: PLoS ONE 5(3)
  • Peer Reviewed
• [Journal Article] Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB1*1501-DQB1*0602 haplotype. (2010)
  • Author(s): Miyagawa T, Honda M, Kawashima M, Shimada M, Tanaka S, Honda Y, Tokunaga K
  • Journal Title: J Hum Gent 55(1) Pages: 63-65
  • NAID: 10030733344
  • Peer Reviewed
• [Journal Article] IgG Abnormality in Narcolepsy and Idiopathic Hypersomnia (2010)
  • Author(s): Tanaka S, Honda M
  • Journal Title: PLoS ONE 5
  • Peer Reviewed
• [Journal Article] Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB1^*1501-DQB1^*0602 haplotype (2010)
  • Author(s): Miyagawa T, Honda M, Kawashima M, Shimada M, Tanaka S, Honda Y, Tokunaga K
  • Journal Title: Journal of human genetics 55 Pages: 63-65
  • NAID: 10030733344
  • Peer Reviewed
• [Journal Article] Absence of Anti-aquaporin-4 Antibody in Narcolepsy. (2009)
  • Author(s): Tanaka S, Kawashima M, Honda M
  • Journal Title: Sleep Biol Rhythms 7 Pages: 66-70
  • Peer Reviewed
• [Journal Article] Polymorphism located between CPT1B and CHKB, and HLA-DRB1*1501-DQB1*0602 haplotype confer susceptibility to CNS hypersomnias (essential hypersomnia) (2009)
  • Author(s): Miyagawa T, Honda M, Kawashima M, Shimada M, Tanaka S, Honda Y, Tokunaga K
  • Journal Title: PLoS ONE 4(4)
  • Peer Reviewed
• [Journal Article] 網羅的遺伝子解析により見いだされたナルコレプシー候補遺伝子の機能解析 (2009)
  • Author(s): 田中進, 本多真, Mignot E
  • Journal Title: 精神薬療研究年報 第41集 Pages: 97-108
• [Journal Article] IGFBP3 colocalizes with and regulates hypocretin (orexin) (2009)
  • Author(s): Honda M, Eriksson KS, Zhang S, Tanaka S, Lin L, Salehi A, Hesla PE, Maehlen J, Gaus SE, Yanagisawa M, Sakurai T, Taheri S, Tsuchiya K, Honda Y, Mignot E
  • Journal Title: PLoS ONE 4(1)
  • Peer Reviewed
• [Journal Article] Absence of Anti-aquaporin-4 Antibody in Narcolepsy (2009)
  • Author(s): Tanaka S, Kawashima M, Honda M
  • Journal Title: Sleep and Biological Rhythms 7 Pages: 66-70
  • Peer Reviewed
• [Journal Article] Novel candidate gene for narcolepsy to regulate orexin expression by comprehensive expression profile. (2009)
  • Author(s): Tanaka S, Honda M, Mignot E
  • Journal Title: Annual report of Pharmacopsychiatry research 41 Pages: 97-108
• [Journal Article] Polymorphism located between CPT1B and CHKB, and HLA-DRB1*1501-DQB1*0602 haplotype confer susceptibility to CNS hypersomnias (essential hypersomnia) (2009)
  • Author(s): Miyagawa T, Honda M, Kawashima M, Shimada M, Tanaka S, Honda Y, Tokunaga K
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] Isotype analysis of human anti-Borna disease virus antibodies in Japanese psychiatric and general population. (2008)
  • Author(s): Matsunaga H, Tanaka S, Fukumori A, Tomonaga K, Ikuta K, Amino N, Takeda M
  • Journal Title: J Clin Virol 43(3) Pages: 317-22
  • Peer Reviewed
• [Journal Article] MX2 Gene Expression Tends to be Downregulated in Subjects with HLA-DQB1*0602. (2008)
  • Author(s): Tanaka S, Honda Y, Honda M
  • Journal Title: Sleep 31(5) Pages: 749-751
  • Peer Reviewed
• [Journal Article] MX2 Gene Expression Tends to be Downregulated in Subjects with HLA-DQB 1*0602. (2008)
  • Author(s): Tanaka S, Honda Y, Honda M.
  • Journal Title: SLEEP 31 Pages: 749-751
  • Peer Reviewed
• [Journal Article] Isotype analysis of human anti-Borna disease virus antibodies in Japanese psychiatric and general population. (2008)
  • Author(s): Matsunaga H, Tanaka S, Fukumori A, Tomonaga K, Ikuta K, Amino N, Takeda M.
  • Journal Title: J Clin Virol 43 Pages: 317-322
  • Peer Reviewed
• [Journal Article] IGFBP3 colooalizes with and regulates hypocretin (orexin). (2008)
  • Author(s): Honda M, Eriksson KS, Zhang S, Tanaka S, Lin L, Salehi A, Hesla PE, Maehlen J, Gaus SE, Yanagisawa M, Sakurai T, Taheri S, Tsuchiya K, Honda Y, Mignot E.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Presentation] NR6A1 regulates hypocretin/orexin transcription in vitro. (2009)
  • Author(s): Tanaka S
  • Organizer: The 3rd Asian Narcolepsy Forum
  • Place of Presentation: Osaka
  • Year and Date: 2009-10-27
• [Presentation] IgG abnormality in narcolepsy and idiopathic hypersomnia. (2009)
  • Author(s): Tanaka S
  • Organizer: The 3rd Asian Narcolepsy Forum
  • Place of Presentation: Osaka
  • Year and Date: 2009-10-27
• [Presentation] IgG abnormality in narcolepsy and idiopathic hypersomnia (2009)
  • Author(s): Tanaka S
  • Organizer: The 3rd Asian Narcolepsy Forum
  • Place of Presentation: Osaka
  • Year and Date: 2009-10-27
• [Presentation] NR6A1 regulates hypocretin/orexin transcription in vitro (2009)
  • Author(s): Tanaka S
  • Organizer: The 3rd Asian Narcolepsy Forum
  • Place of Presentation: Osaka
  • Year and Date: 2009-10-27
• [Presentation] ナルコレプシーにおける抗アクアポリン4抗体のスクリーニング (2009)
  • Author(s): 田中進, 川嶋実苗, 本多真
  • Organizer: 日本睡眠学会第34回定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-10-25
• [Presentation] ラット視床下部におけるオレキシンmRNAの日内変動パターン (2009)
  • Author(s): 田中進, 児玉亨, 本多芳子, 臼井節夫, 本多真
  • Organizer: 日本睡眠学会第34回定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-10-25
• [Presentation] HLA gene expression in white blood cells of narcolepsy. (2009)
  • Author(s): Honda M, Tanaka S, Honda Y
  • Organizer: 23rd annual meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Seattle
  • Year and Date: 2009-06-09
• [Presentation] HLA gene expression in white blood cells of narcolepsy (2009)
  • Author(s): Honda M, Tanaka S, Honda Y
  • Organizer: 23rd annual meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Seattle, USA
  • Year and Date: 2009-06-09
• [Presentation] 網羅的遺伝子発現解析により見いだしたナルコレプシー候補遺伝子の機能解析. (2008)
  • Author(s): 田中進, 本多真, Emmanuel Mignot
  • Organizer: 第41回精神神経系薬物治療研究報告会
  • Place of Presentation: 大阪
  • Year and Date: 2008-12-05
• [Presentation] 網羅的遺伝子発現解析により見いだしたナルコレプシー候補遺伝子の機能解析 (2008)
  • Author(s): 田中進
  • Organizer: 第41回 精神神経系薬物治療研究報告会
  • Place of Presentation: 大阪
  • Year and Date: 2008-12-05
• [Presentation] 視床下部オレキシン発現制御におけるNur77/NR4A1の関与 (2008)
  • Author(s): 田中進, 本多真, 川嶋実苗, 新井誠, 野中隆, 深澤みゆき, Eriksson KS, Lin L, 本多裕, Mignot E
  • Organizer: 日本睡眠学会第33回定期学術集会
  • Place of Presentation: 郡山
  • Year and Date: 2008-06-25
• [Presentation] nsulin-like growth factor binding protein-3 reduces hypocretin/orexin transmission. (2008)
  • Author(s): Zhang S, Lin L, Zhang J, Tanaka S, Honda M, Mignot E
  • Organizer: 22nd annual meeting of the Associated Professional Sleep Societies
  • Place of Presentation: Baltimore
  • Year and Date: 2008-06-07