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Elucidation of the mechanism of promoting dementia caused by diabetes mellitus, focusing on the transport dynamics of glucose through the choroid plexus

Research Project

Project/Area Number 17K08788
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKagawa University

Principal Investigator

Ueno Masaki  香川大学, 医学部, 教授 (30322267)

Co-Investigator(Kenkyū-buntansha) 千葉 陽一  香川大学, 医学部, 講師 (30372113)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords糖輸送体 / 脈絡叢 / 脈絡叢上皮細胞 / SGLT2 / 認知症 / 果糖 / ブドウ糖 / 尿酸 / GLUT / GLUT8 / GLUT9 / URAT1 / 病理学 / 糖尿病
Outline of Final Research Achievements

Urate transporters, GLUT9 and URAT1, which are believed to be related with reduction of oxidative stress, were located on apical and basal cytoplasmic membranes of choroid plexus epithelium (Nerosci Lett 2017, 659, 99-103). An efflux transporter of iron which is related to oxidative damage, ferroportin, as well as hepcidin and hephaestin were located in the cytoplasm of choroid plexus epithelium (Neuropathol 2020, 40, 75-83). In addition, sodium/glucose cotransporter 2 (SGLT2), through which glucose is transported based on sodium concentration gradient, was located in the cytoplasm of choroid plexus epithelium (Neuropathol 2020, in press).

Academic Significance and Societal Importance of the Research Achievements

糖や鉄や尿酸が脈絡叢に存在する輸送体を介して脳内に輸送されていることが明らかになった。酸化ストレスや糖化ストレスに密接に関係しているこれらの物質が脈絡叢に局在する輸送体を介して脳室周囲領域に流入してくれば、その領域に影響を及ぼすであろうことは容易に想像できる。以上から、糖尿病患者の認知機能低下に関与していると考えられる脳室周囲領域における組織傷害にこれらの輸送体を介する物質の移動が関係していると考えられ、その輸送体をターゲットにした糖尿病患者の認知機能低下に対する新規治療法に繋がるものと考えられた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Sodium/glucose cotransporter 2 is expressed in choroid plexus epithelial cells and ependymal cells in human and mouse brains2020

    • Author(s)
      Chiba Yoichi, Sugiyama Yasunori, Nishi Nozomu, Nonaka Wakako, Murakami Ryuta, Ueno Masaki
    • Journal Title

      Neuropathology

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoreactivities for hepcidin, ferroportin, and hephaestin in astrocytes and choroid plexus epithelium of human brains2019

    • Author(s)
      Yanase Ken、Uemura Naoya、Chiba Yoichi、Murakami Ryuta、Fujihara Ryuji、Matsumoto Koichi、Shirakami Gotaro、Araki Nobukazu、Ueno Masaki
    • Journal Title

      Neuropathology

      Volume: 40 Issue: 1 Pages: 75-83

    • DOI

      10.1111/neup.12611

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disturbance of Intracerebral Fluid Clearance and Blood?Brain Barrier in Vascular Cognitive Impairment2019

    • Author(s)
      Ueno Masaki、Chiba Yoichi、Murakami Ryuta、Matsumoto Koichi、Fujihara Ryuji、Uemura Naoya、Yanase Ken、Kamada Masaki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 10 Pages: 2600-2600

    • DOI

      10.3390/ijms20102600

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histomorphometry of ectopic mineralization using undecalcified frozen bone sections2018

    • Author(s)
      Fujihara Ryuji、Chiba Yoichi、Nakagawa Toshitaka、Murakami Ryuta、Matsumoto Koichi、Kawauchi Machi、Fujii Takayuki、Shimono Ryuichi、Yamamoto Tetsuji、Ueno Masaki
    • Journal Title

      Microscopy Research and Technique

      Volume: 81 Issue: 11 Pages: 1318-1324

    • DOI

      10.1002/jemt.23140

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glucose transporter 8 immunoreactivity in astrocytic and microglial cells in subependymal areas of human brains2017

    • Author(s)
      Mashima M, Chiba Y, Murakami R, Uemura N, Matsumoto K, Kawauchi M, Kanenishi K, Hata T, Ueno M
    • Journal Title

      Neuroscience Letters

      Volume: 636 Pages: 90-94

    • DOI

      10.1016/j.neulet.2016.11.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Immunoreactivity of urate transporters, GLUT9 and URAT1, is located in epithelial cells of the choroid plexus of human brains2017

    • Author(s)
      Uemura Naoya、Murakami Ryuta、Chiba Yoichi、Yanase Ken、Fujihara Ryuji、Mashima Masato、Matsumoto Koichi、Kawauchi Machi、Shirakami Gotaro、Ueno Masaki
    • Journal Title

      Neuroscience Letters

      Volume: 659 Pages: 99-103

    • DOI

      10.1016/j.neulet.2017.09.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 血液脳関門障害の機序解明から血管性認知症の治療と予防に向けて2019

    • Author(s)
      上野正樹
    • Organizer
      第3回日本脳神経外科認知症学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 老化と認知症の神経病理:ヒトとSAMマウスの接点を考える2019

    • Author(s)
      千葉陽一
    • Organizer
      第34回老化促進モデルマウス(SAM)学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Expression of transporters of glucose and fructose in epithelial cells of the choroid plexus and ependymal cells of human and mouse brains2018

    • Author(s)
      Yoichi Chiba, Koichi Matsumoto, Murakami Ryuta, Uemura Naoya, Mashima Masato, Yanase Ken, Fujihara Ryuji, Kawauchi Machi, Ueno Masaki
    • Organizer
      19th International Congress of Neuropathology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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