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Functional analysis of Ccr3 associated with narcolepsy

Research Project

Project/Area Number 26870117
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Psychiatric science
Research InstitutionThe University of Tokyo

Principal Investigator

Toyoda Hiromi  東京大学, 大学院医学系研究科(医学部), 客員研究員 (90637448)

Research Collaborator HONDA Yoshiko  
KODAMA Tohru  
TANAKA Susumu  
MIYAGAWA Taku  
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsナルコレプシー / 睡眠 / Ccr3 / ケモカイン受容体 / オレキシン細胞 / 睡眠障害 / CCR3 / ケモカインレセプター / ケモカイン / 神経免疫
Outline of Final Research Achievements

Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. I previously reported CCR3 as a novel susceptibility gene for narcolepsy. This study investigated sleep-wake patterns of Ccr3 KO mice to understand the role of CCR3 in the development of narcolepsy.
Ccr3 KO mice exhibited fragmented sleep patterns in the resting phase. Intraperitoneal injection of LPS promoted wakefulness and suppressed both REM and NREM sleep in the resting phase in both Ccr3 KO and WT mice. These LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice.
We propose that impaired function of Ccr3 causes fragmented sleep that can contribute to vulnerability to developing narcolepsy in an inflammatory context induced by environmental triggers.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016 2015 2014

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Epigenome-wide association study of DNA methylation in narcolepsy: an integrated genetic and epigenetic approach2018

    • Author(s)
      Shimada Mihoko、Miyagawa Taku、Toyoda Hiromi、Tokunaga Katsushi、Honda Makoto
    • Journal Title

      Sleep

      Volume: 41 Issue: 4 Pages: 1-9

    • DOI

      10.1093/sleep/zsy019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.2017

    • Author(s)
      Toyoda H, Honda Y, Tanaka S, Miyagawa T, Honda M, Honda K, Tokunaga K, Kodama T.
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 11 Pages: 1-17

    • DOI

      10.1371/journal.pone.0187888

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of polygenic risks for narcolepsy and essential hypersomnia2016

    • Author(s)
      Yamasaki M, Miyagawa T, Toyoda H, Khor SS, Liu X, Kuwabara H, Kano Y, Shimada T, Sugiyama T, Nishida H, Sugaya N, Tochigi M, Otowa T, Okazaki Y, Kaiya H, Kawamura Y, Miyashita A, Kuwano R, Kasai K, Tanii H, Sasaki T, Honda Y, Honda M, Tokunaga K
    • Journal Title

      Journal of Human Genetics

      Volume: 61(10) Issue: 10 Pages: 873-878

    • DOI

      10.1038/jhg.2016.65

    • NAID

      40020966185

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hypocretin/orexin loss changes the hypothalamic immune response.2016

    • Author(s)
      Tanaka S, Takizawa N, Honda Y, Taro Koike T, Oe S, Hiromi Toyoda H, Kodama T, Hisao Yamada H.
    • Journal Title

      Brain, Behavior, and Immunity

      Volume: 57 Pages: 58-67

    • DOI

      10.1016/j.bbi.2016.06.009

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A polymorphism in CCR1/CCR3 is associated with narcolepsy.2015

    • Author(s)
      Toyoda H, Miyagawa T, Koike A, Kanbayashi T, Imanishi A, Sagawa Y, Kotorii N, Kotorii T, Hashizume Y, Ogi K, Hiejima H, Kamei Y, Hida A, Miyamoto M, Imai M, Fujimura Y, Tamura Y, Ikegami A, Wada Y, Moriya S, Furuya H, Takeuchi M, Kirino Y, Meguro A, Remmers EF, Kawamura Y, Otowa T, Miyashita A, et al.
    • Journal Title

      Brain Behav Immun.

      Volume: 印刷中 Pages: 148-155

    • DOI

      10.1016/j.bbi.2015.05.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypocretin/orexin prevents recovery from sickness.2015

    • Author(s)
      Tanaka S, Toyoda H, Honda Y, Seki Y, Sakurai T, Honda K, Kodama T.
    • Journal Title

      Biomedical Reports

      Volume: 3 Issue: 5 Pages: 648-650

    • DOI

      10.3892/br.2015.491

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] New susceptibility variants to narcolepsy identified in HLA class II region.2015

    • Author(s)
      Miyagawa T, Toyoda H, Hirataka A, Kanbayashi T, Imanishi A, Honda M, Tokunaga K, et al.
    • Journal Title

      Hum. Mol. Genet.

      Volume: 24 Issue: 3 Pages: 891-898

    • DOI

      10.1093/hmg/ddu480

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references.2015

    • Author(s)
      Khor SS, Yang W, Kawashima M, Kamitsuji S, Zheng X, Nishida N, Sawai H, Toyoda H, Miyagawa T, Honda M, Kamatani N, Tokunaga K.
    • Journal Title

      Pharmacogenomics J.

      Volume: 未定 Issue: 6 Pages: 1-8

    • DOI

      10.1038/tpj.2015.4

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Genome-wide analysis of CNV (copy number variation) and their associations with narcolepsy in a Japanese population2014

    • Author(s)
      Yamasaki M, Miyagawa T, Toyoda H, Khor SS, Koike A, Nitta A, Akiyama K, Sasaki T, Honda M, and Tokunaga K
    • Journal Title

      J. Hum. Genet.

      Volume: 印刷中 Issue: 5 Pages: 235-240

    • DOI

      10.1038/jhg.2014.13

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Incrased plasma IL-6, IL-8, TNF-alpha and G-CSF in Japanese narcolepsy.2014

    • Author(s)
      Tanaka S, Honda M, Toyoda H, Kodama T.
    • Journal Title

      Hum. Immunol.

      Volume: 75 Issue: 8 Pages: 940-944

    • DOI

      10.1016/j.humimm.2014.06.023

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] A polymorphism in CCR1/CCR3 is associated with narcolepsy2016

    • Author(s)
      Hiromi Toyoda, Taku Miyagawa, Asako Koike, Seik-Soon Khor, Makoto Honda, Katsushi Tokunaga
    • Organizer
      International Congress of Human Genetics 2016
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-04-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] A polymorphism in CCR1/CCR3 is associated with narcolepsy2015

    • Author(s)
      豊田裕美、宮川卓、Khor Seik Soon、小池麻子、本多真、徳永勝士
    • Organizer
      日本人類遺伝学会 第60回大会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] A polymorphism in CCR1/CCR3 is associated with narcolepsy2015

    • Author(s)
      豊田裕美、宮川卓、Khor Seik Soon、小池麻子、本多真、徳永勝士
    • Organizer
      第27回日本神経免疫学会学術集会
    • Place of Presentation
      長良川国際会議場(岐阜県岐阜市)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 新規ナルコレプシー疾患感受性遺伝子の探索2014

    • Author(s)
      豊田裕美、宮川卓、Khor Seik Soon、川嶋実苗、山崎茉莉亜、小池麻子、田中進、本多裕、本多真、徳永勝士
    • Organizer
      第59回日本人類遺伝学会
    • Place of Presentation
      東京、タワーホール船堀
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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