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Mechanism of increase in brain-aromatic monoamines after peripheral administration of sepiapterin

Research Project

Project/Area Number 16K20429
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional basic dentistry
Research InstitutionNihon University

Principal Investigator

OHASHI Akiko  日本大学, 歯学部, 助教 (00571019)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsセロトニン / ドーパミン / モノアミン合成促進 / テトラヒドロビオプテリン補充 / モノアミン合成 / 抗うつ薬 / テトラヒドロビオプテリン / 薬理学 / 脳神経疾患 / 生理活性 / 脳・神経 / モノアミン
Outline of Final Research Achievements

Serotonin (5HT) biosynthesis in the brain is controlled by tetrahydrobiopterin (BH4) level. Peripheral dosing of sepiapterin (SP) as a prodrug of BH4 to mice showed significant rise in BH4, 5HT, DA and their metabolites in the brain time- and dose-dependently. 5HT synthesis in a culture cell was promoted by added SP in the medium, while more than 20-fold higher concentration of BH4 was required for the same enhancement. SP showed adequate permeation across in vitro BBB model. These results suggested that not-all SP converted to BH4 in the periphery but partly reached the brain as SP.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results)

  • [Journal Article] Organic anion transporters, OAT1 and OAT3, are crucial biopterin transporters involved in bodily distribution of tetrahydrobiopterin and exclusion of its excess2017

    • Author(s)
      Ohashi Akiko、Mamada Kaori、Harada Tomonori、Naito Masako、Takahashi Tomihisa、Aizawa Shin、Hasegawa Hiroyuki
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 435 Issue: 1-2 Pages: 97-108

    • DOI

      10.1007/s11010-017-3060-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism2017

    • Author(s)
      Oguri Yasuo、Fujita Yoshihito、Abudukadier Abulizi、Ohashi Akiko、Goto Tsuyoshi、Furuya Futoshi、Obara Akio、Fukushima Toru、Matsuo Naomi、Kim Minji、Hosokawa Masaya、Kawada Teruo、Hasegawa Hiroyuki、Inagaki Nobuya
    • Journal Title

      JCI Insight

      Volume: 2 Issue: 9 Pages: 91981-91981

    • DOI

      10.1172/jci.insight.91981

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tetrahydrobiopterin Supplementation: Elevation of Tissue Biopterin Levels Accompanied by a Relative Increase in Dihydrobiopterin in the Blood and the Role of Probenecid-Sensitive Uptake in Scavenging Dihydrobiopterin in the Liver and Kidney of Rats.2016

    • Author(s)
      Ohashi A, Saeki Y, Harada T, Naito M, Takahashi T, Aizawa S, Hasegawa H.
    • Journal Title

      PLoS One.

      Volume: 11 Issue: 10 Pages: e0164305-e0164305

    • DOI

      10.1371/journal.pone.0164305

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] セピアプテリンの末梢投与による脳内トリプトファンレベルの変動2017

    • Author(s)
      大橋晶子,原田智紀,内藤昌子,髙橋富久,相澤信,長谷川宏幸
    • Organizer
      日本ビタミン学会第69回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 有機陰イオン輸送体はBH4の尿中排出に関わる2017

    • Author(s)
      大橋晶子,内藤昌子,髙橋富久,原田智紀,長谷川宏幸
    • Organizer
      第31回日本プテリジン研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] テトラヒドロビオプテリンの尿中排出への有機陰イオン輸送体の関与2017

    • Author(s)
      大橋晶子,内藤昌子,髙橋富久
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肥満細胞におけるテトラヒドロビオプテリンによるセロトニン生合成の促進2016

    • Author(s)
      大橋晶子, 笠原正彰, 内藤昌子, 髙橋富久
    • Organizer
      第58回歯科基礎医学会学術大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] セピアプテリンの末梢投与による脳内カテコールアミン生合成の促進2016

    • Author(s)
      大橋晶子, 内藤昌子, 髙橋富久, 原田智紀, 長谷川宏幸
    • Organizer
      日本ビタミン学会第68回大会
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 細胞外のテトラヒドロビオプテリンがセロトニン生合成活性に与える影響2016

    • Author(s)
      大橋晶子, 原田智紀, 内藤昌子, 髙橋富久, 相澤信, 長谷川宏幸
    • Organizer
      第20回活性アミンに関するワークショップ
    • Place of Presentation
      ホテルマークワンつくば研究学園(茨城県つくば市)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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