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Vitamin B12 metabolism and its relation for neural and cognitive functions

Research Project

Project/Area Number 15K07770
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionOsaka Prefecture University

Principal Investigator

Takenaka Shigeo  大阪府立大学, 総合リハビリテーション学研究科, 教授 (10280067)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsビタミンB12 / 神経細胞 / 認知機能 / 欠乏 / 神経疾患 / 代謝異常 / 神経細胞分化 / 酸化ストレス / RNAi / CRISPR/CAS9 / 赤芽球
Outline of Final Research Achievements

It has been reported that vitamin B12 (Cobalamin, B12) might be a risk factor for cognitive function in elderly people, but its biochemical and molecular mechanisms are remained unclear. Here I examined the mechanism with a neural stem cells which knockdown or knockout its B12 metabolize enzymes and with a B12 and/or folate-deficient mice model.
The cbl genes which are B12-metabolizing protein coding genes, in SH-SY5Y cell, a model cell of neurite formation, were down-regulated with a RNAi plasmid or edited CRISR/CAS9 system. The dendrites formation induced by all trans retinoic acid were inhibited and the formation of actin filaments under the dendrites were reduced in the cells. The learning ability was significantly reduced in the B12 and folate-deficient mice.
In conclusion, B12-deficiency might reduce the learning ability in mice and might be involved in the neural cell differentiation and their viability.

Report

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

    (11 results)

All 2018 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results) Presentation (8 results)

  • [Journal Article] Cytochrome P450 2A6 and other human P450 enzymes in the oxidation of flavone and flavanone2018

    • Author(s)
      Kakimoto Kensaku、Murayama Norie、Takenaka Shigeo、Nagayoshi Haruna、Lim Young-Ran、Kim Vitchan、Kim Donghak、Yamazaki Hiroshi、Komori Masayuki、Guengerich F. Peter、Shimada Tsutomu
    • Journal Title

      Xenobiotica

      Volume: 48 Issue: 2 Pages: 1-12

    • DOI

      10.1080/00498254.2018.1426133

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oxidation of 1-chloropyrene by human CYP1 family and CYP2A subfamily cytochrome P450 enzymes: catalytic roles of two CYP1B1 and five CYP2A13 allelic variants2017

    • Author(s)
      Shimada Tsutomu、Murayama Norie、Kakimoto Kensaku、Takenaka Shigeo、Lim Young-Ran、Yeom Sora、Kim Donghak、Yamazaki Hiroshi、Guengerich F. Peter、Komori Masayuki
    • Journal Title

      Xenobiotica

      Volume: 49 Issue: 6 Pages: 1-11

    • DOI

      10.1080/00498254.2017.1347306

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Profiling of plasma metabolites in canine oral melanoma using gas chromatography-mass spectrometry2015

    • Author(s)
      Kawabe, M., Baba, Y., Tamai, R., Yamamoto, R., Komori, M., Takenaka, S.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 77 Issue: 8 Pages: 1025-1028

    • DOI

      10.1292/jvms.14-0641

    • NAID

      130005094686

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] ビタミンB12代謝異常がヒト慢性骨髄性白血病細胞の分化に及ぼす影響2017

    • Author(s)
      巨海竜一、平岩 悟、小柳友和、小森雅之、竹中重雄
    • Organizer
      日本ビタミン学会第69回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 食餌による葉酸とビタミンB12欠乏モデルマウス作製の試み2017

    • Author(s)
      小栁 友和、平岩 悟、小森雅之、竹中重雄
    • Organizer
      第160回日本獣医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CRISPR/Cas9法によるビタミンB12代謝関連遺伝子ノックアウト細胞作製2017

    • Author(s)
      平岩 悟、小栁 友和、小森雅之、竹中重雄
    • Organizer
      第160回日本獣医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ビタミンB12代謝異常と低酸素による慢性骨髄性白血病細胞分化への影響2016

    • Author(s)
      海竜一,平岩悟,小柳友和,小森雅之,竹中重雄
    • Organizer
      日本獣医学会
    • Place of Presentation
      日本大学資源科学部(湘南キャンパス)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト神経芽腫細胞SH-SY5YにおけるビタミンB12代謝異常と酸化ストレス2016

    • Author(s)
      竹中重雄,山木隆裕,巨海竜一,小森雅之
    • Organizer
      日本ビタミン学会
    • Place of Presentation
      富山国際会議場
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] ビタミンB12代謝異常と酸化ストレスのヒト神経芽腫細胞への影響2015

    • Author(s)
      山木隆裕,巨海竜一,小森雅之,竹中重雄
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] ビタミンB12代謝遺伝子RNAiはヒト神経芽腫細胞のストレス感受性を増加させる2015

    • Author(s)
      山木隆裕、巨海竜一、小森雅之、竹中重雄
    • Organizer
      第158回日本獣医学会学術集会
    • Place of Presentation
      北里大学獣医学部(青森県十和田市)
    • Year and Date
      2015-09-07
    • Related Report
      2015 Research-status Report
  • [Presentation] 先天性ビタミンB12代謝異常症遺伝子群RNAiによるヒト神経芽腫細胞の分化抑制2015

    • Author(s)
      山木隆裕、馬場雄大、巨海竜一、小森雅之、竹中重雄、渡辺文雄、中野長久
    • Organizer
      日本ビタミン学会第66回大会
    • Place of Presentation
      奈良県新公会堂(奈良県奈良市)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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