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Astrocytic neuroprotective mechanism against diabetic encephalopathy through metabolic stress response

Research Project

Project/Area Number 24591276
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKeio University

Principal Investigator

TAKAHASHI Shinichi  慶應義塾大学, 医学部, 准教授 (20236285)

Research Collaborator ABE Takato  大阪市立大学, 大学院医学研究科, 講師 (30365233)
IZAWA Yoshikane  慶應義塾大学, 医学部, 助教 (90468471)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords糖尿病 / 認知症 / アストロサイト / アストログリア / 高血糖 / 酸化ストレス / ペントースリン酸経路 / ケトン体 / astroglia / Keap1/Nrf2 / PPP / LPS / TLR4 / ER stress / glycolysis
Outline of Final Research Achievements

Astroglia play a pivotal role in the brain glucose metabolism. In particular, the astroglial metabolic compartment exerts supportive roles in making neurons dedicated to generating action potentials and protects them against oxidative stress associated with high energy consumption. Thus, the metabolic responses of the astroglia in patients with diabetes mellitus (DM) would be neuro-protective. DM induces numerous metabolic derangements, resulting in irreversible neuronal damage. Therefore, the metabolic responses of the astroglia in the early stage of DM could be either protective or deleterious. In this project, we focused on three major metabolic responses: 1) glucose, 2) inflammatory 3) fatty acid. A better understanding of the astroglial metabolic response in normal physiological state may be expected to lead to the development of a novel strategy in DM-associated encephalopathy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (5 results) (of which Invited: 5 results) Book (1 results)

  • [Journal Article] Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia.2014

    • Author(s)
      Takahashi S, Iizumi T, Mashima K, Abe T, Suzuki, N.
    • Journal Title

      ASN Neuro

      Volume: 6(5) Issue: 5 Pages: 1-1

    • DOI

      10.1177/1759091414550997

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular origin and regulation of D- and L-serine in vitro and in vivo models of cerebral ischemia.2014

    • Author(s)
      Abe T, Suzuki M, Sasabe J, Takahashi S, Unekawa M, Mashima K, Iizumi T, Hamase K, Konno R, Aiso S, Suzuki N.
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 34(12) Issue: 12 Pages: 1928-1935

    • DOI

      10.1038/jcbfm.2014.164

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subsequent vascular events after ischemic stroke: the Japan Statin Treatment Against Recurrent Stroke-Longitudinal.2014

    • Author(s)
      Nomura E, Suzuki A, Inoue I, Nakagawara L, Takahashi K, Takahashi T, Manabe Y, Yokota C, Okada K, Nishihara T, Yamamoto Y, Noda K, Takahashi S, Ibayashi S, Takagi M, Kitagawa K, Tanahashi N, Kuriyama M, Hirata K, Hosomi N, Minematsu K, Kobayashi K, Matsumoto M.
    • Journal Title

      J Stroke Cerebrovasc Dis

      Volume: 24(2) Issue: 2 Pages: 473-9

    • DOI

      10.1016/j.jstrokecerebrovasdis.2014.09.023

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of metabolic compartmentalization by astrocytes and neurons in the pathophysiology and treatment of Parkinson’s disease2013

    • Author(s)
      Shinichi Takahashi, Morinobu Seki, Norihiro Suzuki
    • Journal Title

      Brain and Nerve

      Volume: 65(2) Pages: 1497-1508

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] NVUにおけるBBBの役割とcellular metabolic compartment2013

    • Author(s)
      髙橋愼一、安部貴人、伊澤良兼、飯泉琢矢、鈴木則宏
    • Journal Title

      脳循環代謝

      Volume: 24 Pages: 75-82

    • Related Report
      2013 Research-status Report
  • [Journal Article] 脳血管とアストロサイト-neurovascular unitの概念について-2013

    • Author(s)
      髙橋愼一
    • Journal Title

      神経内科

      Volume: 79(2) Pages: 247-5

    • Related Report
      2013 Research-status Report
  • [Journal Article] 血液脳関門および脳循環・代謝調節とアストロサイト2013

    • Author(s)
      髙橋愼一
    • Journal Title

      実験医学

      Volume: 31(14) Pages: 2195-2203

    • Related Report
      2013 Research-status Report
  • [Journal Article] Neurovascular unit: NVU2013

    • Author(s)
      髙橋愼一
    • Journal Title

      分子脳血管病

      Volume: 12(4)

    • Related Report
      2013 Research-status Report
  • [Journal Article] Astrogliopathy as a loss of astroglial protective function against glycoxidative stress under hyperglycemia2012

    • Author(s)
      Shinichi Takahashi, Yoshikane Izawa, Norihiro Suzuki
    • Journal Title

      Rinsho Shinkeigaku

      Volume: 52 Issue: 1 Pages: 41-51

    • DOI

      10.5692/clinicalneurol.52.41

    • NAID

      130004505025

    • ISSN
      0009-918X, 1882-0654
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of fluctuating glucose concentrations on oxidative metabolism of glucose in cultured neurons and astroglia.2012

    • Author(s)
      Shinichi Takahashi, Yoshikane Izawa, Norihiro Suzuki
    • Journal Title

      Journal of Diabetes Mellitus

      Volume: 2(1) Issue: 01 Pages: 19-26

    • DOI

      10.4236/jdm.2012.21004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Astroglial pentose phosphate pathway rates in response to high-glucose environments.2012

    • Author(s)
      Shinichi Takahashi, Yoshikane Izawa, Norihiro Suzuki
    • Journal Title

      ASN NEURO

      Volume: 4(2) Issue: 2

    • DOI

      10.1042/an20120002

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] CBF/Neurovascular Unit; metabolic balance of neuron.2015

    • Author(s)
      Takahashi S.
    • Organizer
      The XXVIIth International Symposium on Cerebral Blood Flow, Metabolism and Function & XIIth International Conference on Quantification of Brain Function with PET
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2015-06-27 – 2015-06-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] アストログリアをターゲットとした脳梗塞治療戦略の構築2014

    • Author(s)
      髙橋愼一
    • Organizer
      第26 回日本脳循環代謝学会総会シンポジウム3
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2014-11-21 – 2014-11-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] アストロサイト研究の現状と展望2013

    • Author(s)
      高橋愼一
    • Organizer
      第25回日本脳循環代謝学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 脳梗塞急性期治療:Tissue clock と Reperfusion.2012

    • Author(s)
      高橋慎一
    • Organizer
      日本麻酔科学会 第59回学術集会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] アストロサイトとニューロンの代謝からみたパーキンソン病の病態.2012

    • Author(s)
      高橋慎一
    • Organizer
      第6回 パーキンソン病・運動障害コングレス
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] Annual Review 神経2015 中毒・代謝疾患 神経細胞およびグリア細胞におけるケトン体代謝の重要性2015

    • Author(s)
      髙橋愼一
    • Total Pages
      100
    • Publisher
      中外医学社(東京)
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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