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Elucidation of the molecular mechanisms and physiological significance of the structural stabilization of neural networks by neurotrophins

Research Project

Project/Area Number 21700384
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Nerve anatomy/Neuropathology
Research InstitutionFujita Health University

Principal Investigator

OHIRA Koji  Fujita Health University, 総合医科学研究所, 講師 (80402832)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords脳由来神経栄養因子(BDNF) / TrkB / レンチウイルスベクター / RNAi / 神経回路 / 大脳皮質 / 神経可塑性 / 細胞形態 / BDNF受容体TrkB
Research Abstract

The aim of this present study is the clarification of the molecular mechanisms and physiological significance of the stabilization of neural networks by analyzing the subtypes of brain-derived neurotrophic factor (BDNF) receptor TrkB. To achieve this purpose, first of all, I made the lentivirus vectors which expressed siRNAs of TrkB subtypes that were able to interfere with the expression of TrkB subtypes. In addition, the anti-T1 antibody was made to detect whether the knockdown of T1 at the protein level occurred, and I obtained an excellent antibody for T1.
Next, to establish an injection method of the lentivirus vectors into the cerebral ventricles of the fetals, I performed injections of the vectors at various conditions. However, the developments of the embryos after the injection have not advanced well. On the other hand, when the neocortical neurons at P7 or the primary cultures of neocortical neurons were infected with the vectors, I found that the dendritic processes of neurons infected with T1 siRNA virus vectors became long and the number of the branching points of neuronal processes increased.
We have clarified that GABAergic neurons are generated from layer 1 inhibitory neuron progenitor cells (L1-INP cell) by ischemia (Ohira et al., Nature Neuroscience 2010). There are two TrkB receptor subtypes in the mammalian CNS. The full-length isoform TK+ is a typical tyrosine kinase receptor. In contrast, the truncated isoform T1 possesses the isoform specific 11 amino acids in the intracellular domain. Interestingly, T1 was expressed in almost all L1-INP cells, whereas the ratio of L1-INP cells expressing TK+ was low, suggesting that T1 plays a role in the proliferation and differentiation of L1-INP cells.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (22 results)

All 2011 2010 2009 Other

All Journal Article (14 results) (of which Peer Reviewed: 13 results) Presentation (5 results) Remarks (3 results)

  • [Journal Article] Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice.2011

    • Author(s)
      Ohira K, Miyakawa T.
    • Journal Title

      Molecular Brain 4

      Pages: 10-10

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Injury-induced neurogenesis in the mammalian forebrain.2011

    • Author(s)
      Ohira K.
    • Journal Title

      Cellular and Molecular Life Sciences 68

      Pages: 1645-1656

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Injury-induced neurogenesis in the mammalian forebrain.2011

    • Author(s)
      Ohira K.
    • Journal Title

      Cellular and Molecular Life Science

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice.2011

    • Author(s)
      Ohira K, Miyakawa T.
    • Journal Title

      Molecular Brain

      Volume: 4 Pages: 10-10

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus.2010

    • Author(s)
      Ohira K, Hagihara H, Toyama K, Takao K, Kanai M, Funakoshi H, Nakamura T, Miyakawa T.
    • Journal Title

      Molecular Brain 3

      Pages: 26-26

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells.2010

    • Author(s)
      Ohira K, Furuta T, Hioki H, Nakamura KC, Kuramoto E, Tanaka Y, Funatsu N, Shimizu K, Oishi T, Hayashi M, Miyakawa T, Kaneko T, Nakamura S.
    • Journal Title

      Nature Neuroscience 13

      Pages: 173-179

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Injection of virus vectors into the neocortical layer 1.2010

    • Author(s)
      Ohira K, Kaneko T.
    • Journal Title

      Protocol exchange 21

    • Related Report
      2010 Final Research Report
  • [Journal Article] Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus.2010

    • Author(s)
      Ohira K, et al.
    • Journal Title

      Molecular Brain

      Volume: 3 Pages: 26-26

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells2010

    • Author(s)
      Ohira K, et al.
    • Journal Title

      Nature Neuroscience 13

      Pages: 173-179

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Injection of virus vectors into the neocortical layer 1.2010

    • Author(s)
      Ohira K, Kaneko T.
    • Journal Title

      Nature Protocols 10.1038/nprot.2010.21

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new aspect of the TrkB signaling pathway in neural plasticity.2009

    • Author(s)
      Ohira K, Hayashi M.
    • Journal Title

      Current Neuropharmacology 7

      Pages: 276-285

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice.2009

    • Author(s)
      Matsuo N, Yamasaki N, Ohira K, Takao K, Toyama K, Eguchi M, Yamaguchi S, Miyakawa T.
    • Journal Title

      Frontiers in Behavioral Neuroscience 3

      Pages: 20-20

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new aspect of the TrkB signaling pathway in neural plasticity2009

    • Author(s)
      Ohira K, Hayashi M.
    • Journal Title

      Current Neuropharmacology 7

      Pages: 276-285

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice2009

    • Author(s)
      Matsuo N, et al.
    • Journal Title

      Frontiers in behavioral neuroscience 3

      Pages: 20-20

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 海馬歯状回の顆粒細胞におけるTDO2の発現2010

    • Author(s)
      大平耕司、萩原英雄、遠山桂子、高雄啓三、金井将昭、船越洋、中村敏一、宮川剛
    • Organizer
      第33回日本神経科学大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Expression of Tryptophan 2,3-Dioxygenase in Mature Granule Cells of the Adult Mouse Dentate Gyrus2010

    • Author(s)
      大平耕司, 他7名
    • Organizer
      第33回日本神経科学大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] 成熟期大脳皮質に存在する神経前駆細胞2009

    • Author(s)
      大平耕司、古田貴寛、日置寛之、中村公一、倉本恵梨子、船津宣雄、清水慶子、大石高生、林基治、宮川剛、金子武嗣、中村俊
    • Organizer
      第32回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-09-17
    • Related Report
      2010 Final Research Report
  • [Presentation] 成熟期大脳皮質に存在する神経前駆細胞2009

    • Author(s)
      大平耕司, 他11名
    • Organizer
      第32回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2009-09-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Ischemia-induced neurogenesis of endogenous progenitor cells in the neocortex2009

    • Author(s)
      大平耕司, et al.
    • Organizer
      The 36^<th> Congress of the International Union of Physiological Sciences
    • Place of Presentation
      京都国際会議場(京都府)
    • Year and Date
      2009-07-30
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://dsm.fujita-hu.ac.jp/

    • Related Report
      2010 Final Research Report
  • [Remarks] 藤田保健衛生大学・総合医科学研究所・システム医科学

    • URL

      http://dsm.fujita-hu.ac.jp

    • Related Report
      2010 Annual Research Report
  • [Remarks] 藤田保健衛生大学・総合医科学研究所・システム医科学

    • URL

      http://dsm.fujita-hu.ac.jp

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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