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Hippocampus-synthesized brain steroids rapidly modulate neuronal synapses and memory

Research Project

Project/Area Number 18K06526
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionJuntendo University (2020)
Teikyo University (2018)

Principal Investigator

Kawato Suguru  順天堂大学, 医学部, 客員教授 (50169736)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords神経内分泌学 / 神経ステロイド / 海馬 / シナプス / 記憶 / 男性ホルモン / 女性ホルモン / 神経シナプス / 記憶学習 / 脳ステロイド / 性ホルモン / nongenomic
Outline of Final Research Achievements

Sex-steroids rapidly and non-genomically modulated the dendritic spines in the rat hippocampus. We analyzed the molecular mechanisms of these modulations by using 3-dimentional super-resolution confocal microscopic imaging of neuronal synapses. Upon application of male hormones (T and DHT) and female hormones (E2 PROG) for 2 h, the density of dendritic spines were significantly increased. The signal pathways of these modulations were as follows: “binding of sex-steroids to their membrane steroid receptors AR, ER, PR in spines → phosphorylation of kinases such as LIMK, MAPK, PKA, PKC → phosphorylation of cofilin and cortactin → actin polymerization → spine increase”. These networks are working not only in CA1 region (spatial memory) but also in DG region (adult neurogenesis).

Academic Significance and Societal Importance of the Research Achievements

脳ステロイドの神経シナプスのモジュレータとしての研究は大進展している。我々の別の研究などと合わせて、海馬が自前で性ホルモンを局所合成して、その近傍の神経シナプスの急性的な増加作用を引き起こすという地産地消の概念が生まれた。これらのnon-genomic作用とステロイドのgenomicな古典的な作用は共存している。最近、膜受容体のみを欠損させnon-genomic作用のみを止めるマウスもできて、急性と慢性作用の違いや両者の相乗作用が必要であることもわかってきた。non-genomic作用は、世界の学会や論文でステロイドの基本的な作用として認識されて、欠かせない作用として評価されるようになった。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report

Research Products

(23 results)

All 2021 2020 2019 2018 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Rapid effects of estradiol on dendritic spines and synaptic plasticity in the male and female hippocampus2020

    • Author(s)
      Kato A, Murakami G, Hojo Y, Horie S and Kawato S
    • Journal Title

      Estrogens and Memory: Basic Research and Clinical Implications, Oxford Univ. Press

      Volume: Chap 3 Pages: 38-47

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Co-Immunoprecipitation Methods to Identify Associated Proteins with Estrogen Receptor α at Postsynaptic Density in Brain Tissue2019

    • Author(s)
      Murakami G and Kawato S
    • Journal Title

      Neuromethod

      Volume: 144 Pages: 9-21

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 男性ホルモンと海馬認知機能2019

    • Author(s)
      川戸 佳
    • Journal Title

      臨床泌尿器科

      Volume: 73 Pages: 44-48

    • Related Report
      2018 Research-status Report
  • [Journal Article] Ingested D-aspartate facilitates the functional connectivity and modifies dendritic spine morphology in rat hippocampus2018

    • Author(s)
      Kitamura A, Hojo Y, Ikeda M, Karakawa S, Kuwahara T, Kim J, Soma M, Kawato S and Tsurugizawa T
    • Journal Title

      Cerebral Cortex

      Volume: bhy120

    • DOI

      10.1093/cercor/bhy120

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neurosteroids in adult hippocampus of male and female rodents: biosynthesis and actions of sex steroids2018

    • Author(s)
      Hojo Y and Kawato S
    • Journal Title

      Frontiers in Endocrinology

      Volume: 9

    • DOI

      10.3389/fendo.2018.00183

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Src kinase dependent rapid non-genomic modulation of hippocampal spinogenesis induced by androgen and estrogen2018

    • Author(s)
      Soma M, Kim J, Kato A and Kawato S
    • Journal Title

      Frontiers in Neuroscience

      Volume: 12

    • DOI

      10.3389/fnins.2018.00282

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modulation of AKR1C2 by Curcumin Decreases Testosterone Production in Prostate Cancer2018

    • Author(s)
      Ide H, Lu Y, Noguchi T, Muto S, Okada H, Kawato S and Horie S
    • Journal Title

      Cancer Sci.

      Volume: 109 Pages: 1230-1238

    • DOI

      10.1111/cas.13517

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 海馬を中心とした神経内分泌と抗加齢2018

    • Author(s)
      川戸 佳
    • Journal Title

      腎泌尿器疾患予防医学研究会誌

      Volume: 26 Pages: 10-14

    • Related Report
      2018 Research-status Report
  • [Presentation] Hippocampus-synthesized estrogen and androgen modulate dendritic spines and LTP in non-genomic manner2021

    • Author(s)
      Kawato S, Soma M and Ogiue-Ikeda M
    • Organizer
      International Meeting of Steroids and Nervous System
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳海馬が合成する男性・女性ホルモンによる記憶シナプスの急性的制御2020

    • Author(s)
      相馬ミカ、池田真理、川戸佳
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脳海馬が合成する男性・女性ホルモンによる記憶シナプスの急性的制御2020

    • Author(s)
      相馬ミカ、池田真理、川戸佳
    • Organizer
      第20回日本抗加齢医学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 海馬で合成される男性・女性ホルモンやストレスホルモンによる記憶シナプスのnon-genomicな制御2020

    • Author(s)
      川戸佳、相馬ミカ、池田真理、斎藤稔
    • Organizer
      第58回日本生物物理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 男女で記憶中枢・海馬はどう異なるか?性ホルモンの立場から2019

    • Author(s)
      川戸佳
    • Organizer
      性差医学・医療学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 海馬を中心とした神経内分泌と抗加齢2018

    • Author(s)
      川戸佳
    • Organizer
      泌尿器科学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 脳海馬が合成する男性・女性ホルモンによる記憶シナプスの急性的制御2018

    • Author(s)
      相馬ミカ 川戸佳
    • Organizer
      抗加齢医学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳海馬が合成する男性・女性ホルモンによる記憶シナプスの急性的制御2018

    • Author(s)
      相馬ミカ 川戸佳
    • Organizer
      Men’s Health医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳海馬が合成する男性・女性ホルモンによる記憶シナプスの急性的制御2018

    • Author(s)
      相馬ミカ 川戸佳
    • Organizer
      神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 海馬で合成される男性・女性ホルモンやストレスホルモンによる記憶シナプスのnon-genomicな制御2018

    • Author(s)
      相馬ミカ 川戸佳
    • Organizer
      生物物理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳海馬が合成する男性・女性ホルモンによる記憶シナプスの急性的制御2018

    • Author(s)
      相馬ミカ 川戸佳
    • Organizer
      日本神経内分泌学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Hippocampus-synthesized estrogen and androgen modulate dendritic spines and LTP in non-genomic manner2018

    • Author(s)
      Kawato S, Mika Soma and Ogiue-Ikeda M
    • Organizer
      北米神経科学会 (Society for Neuroscience)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脳海馬が合成する男性・女性ホルモンによる膜受容体を介した記憶シナプスの急性的制御2018

    • Author(s)
      相馬ミカ 川戸佳
    • Organizer
      海馬と高次脳機能学会
    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      http://kawato-glia.sakura.ne.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 川戸研究室

    • URL

      http://kawato-glia.sakura.ne.jp/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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