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A novel therapeutic strategy for ischemic stroke based on understanding adult neurogenesis

Research Project

Project/Area Number 15K14335
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionNara Medical University

Principal Investigator

Tsuboi Akio  奈良県立医科大学, 医学部, 教授 (20163868)

Co-Investigator(Kenkyū-buntansha) 高橋 弘雄  奈良県立医科大学, 医学部, 講師 (20390685)
吉原 誠一  奈良県立医科大学, 医学部, 講師 (90360669)
Research Collaborator FUJIOKA Masayuki  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords神経科学 / 脳・神経 / 脳神経疾患 / 再生医学 / 成体神経新生 / 脳梗塞モデルマウス / ニューロン生存 / 神経回路形成 / ニューロン細胞死
Outline of Final Research Achievements

We explored cerebral infarction using a model mouse with an operation of middle cerebral artery occlusion (MCAO) and screened the genes which expressions were altered between the normal and infarct sides in the cerebral cortex two hours after MCAO by RNA sequencing. We narrowed down 27 genes whose expressions were increased in the border of the infarct site compared with the control by ISH. Among these, the neural activity-dependent transcription factor Npas4 showed conspicuous expression in excitatory neurons of the cerebral cortex and the expression pattern that go along the border of the infarct site. Further analyses suggested that Npas4 and its regulating genes play crucial roles in rebuilding the neural circuitry via promoting the neuronal development and survival in the healthy and diseased brain, respectively.

Report

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

    (35 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 6 results) Presentation (15 results) (of which Int'l Joint Research: 10 results,  Invited: 2 results) Book (2 results) Remarks (4 results)

  • [Int'l Joint Research] The University of Manchester(United Kingdom)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Manchester(United Kingdom)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Kantonsspital Aarau(Switzerland)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Olfactory Habituation-dishabituation Test (Mouse)2017

    • Author(s)
      Takahashi H and Tsuboi A
    • Journal Title

      Bio-Protocol

      Volume: 7 Issue: 5

    • DOI

      10.21769/bioprotoc.2154

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Olfactory Avoidance Test (Mouse)2017

    • Author(s)
      Takahashi H and Tsuboi A
    • Journal Title

      Bio-Protocol

      Volume: 7 Issue: 5 Pages: 8210-8227

    • DOI

      10.21769/bioprotoc.2153

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transcription factor Npas4 regulates the development of dendritic spines in newborn olfactory bulb interneurons depending on sensory experience2016

    • Author(s)
      吉原誠一,坪井昭夫
    • Journal Title

      生化学

      Volume: 88 Issue: 2 Pages: 220-224

    • DOI

      10.14952/SEIKAGAKU.2016.880220

    • NAID

      40020843392

    • ISSN
      0037-1017
    • Year and Date
      2016-04-25
    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A subtype of olfactory bulb interneurons is required for odor detection and discrimination behaviors2016

    • Author(s)
      Takahashi H, Ogawa Y, Yoshihara S, Asahina R, Kinoshita M, Kitano T, Kitsuki M, Tatsumi K, Okuda M, Tatsumi K, Wanaka A, Hirai H, Stern PL and Tsuboi A
    • Journal Title

      The Journal of Neuroscience

      Volume: 36 Issue: 31 Pages: 8210-8227

    • DOI

      10.1523/jneurosci.2783-15.2016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Distorted coarse axon targeting and reduced dendrite connectivity underlie dysosmia after olfactory axon2016

    • Author(s)
      Murai A, Iwata R, Fujimoto S, Aihara S, Tsuboi A, Muroyama Y, Saito T, Nishizaki K and Imai T
    • Journal Title

      eNeuro

      Volume: 3 Issue: 5 Pages: 1-13

    • DOI

      10.1523/eneuro.0242-16.2016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 嗅球介在ニューロンのサブタイプが匂いの検出と識別という嗅覚行動に必須な役割を果たす2016

    • Author(s)
      高橋弘雄、坪井昭夫
    • Journal Title

      AROMA RESEARCH

      Volume: 17 Pages: 336-337

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of a filament perforation model for mouse subarachnoid hemorrhage using 7.0 Tesla MRI2016

    • Author(s)
      Muroi C, Kashiwagi Y, Rokugawa T, Tonomura M, Obata A, Nevzati E, Tsuboi A, Okuchi K, Mishima K, Abe K, Fujioka M
    • Journal Title

      J Clin Neurosci.

      Volume: 28 Pages: 141-147

    • DOI

      10.1016/j.jocn.2015.10.045

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Molecular mechanisms regulating the dendritic development of newborn olfactory bulb interneurons in a sensory experience-dependent manner.2016

    • Author(s)
      Yoshihara S, Takahashi H and Tsuboi A.
    • Journal Title

      Frontiers in Neuroscience

      Volume: 9 Pages: 514-514

    • DOI

      10.3389/fnins.2015.00514

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Supersensitive odor discrimination is controlled in part by initial transient interactions between the most sensitive dorsal olfactory receptors and G-proteins2016

    • Author(s)
      Sato T, Kobayakawa R, Kobayakawa K, Emura M, Itohara S, Kawasaki T, Tsuboi A, Matsumura H
    • Journal Title

      Receptors & Clinical Investigation

      Volume: 3

    • DOI

      10.14800/rci.1117

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding2015

    • Author(s)
      Sato T, Kobayakawa R, Kobayakawa K, Emura M, Itohara S, Kizumi M, Hamana H, Tsuboi A, Hirono J
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 14073-14073

    • DOI

      10.1038/srep14073

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 嗅覚系におけるCO2センシングの分子機構2015

    • Author(s)
      高橋弘雄,坪井昭夫
    • Journal Title

      におい・かおり環境学会誌

      Volume: 46 Pages: 209-217

    • NAID

      130007602381

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Neural activity-dependent transcription factor Npas4 plays a crucial role in neuronal survival after ischemic stroke2018

    • Author(s)
      Takahashi H, Asahina R, Fujioka M, Tsuboi A
    • Organizer
      The 22nd Biennial Meeting of the International Society of Developmental Neuroscience
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neural activity-dependent transcription factor Npas4 plays a crucial role in neuronal survival after ischemic stroke2018

    • Author(s)
      Takahashi H, Asahina R, Yoshihara S and Tsuboi A
    • Organizer
      Keystone Symposia: State of the Brain - Genetic Dissection of Brain Circuits and Behavior in Health and Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neural activity-dependent transcription factor Npas4 plays a crucial role in neuroprotection and survival after ischemic stroke2017

    • Author(s)
      Tsuboi A, Asahina R, Yoshihara S and Takahashi H
    • Organizer
      Cortical Development Conference 2017
    • Place of Presentation
      Chania, Crete, Greece
    • Year and Date
      2017-05-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neural activity-induced transcription factor Npas4 is required for neuroprotection and survival after stroke2017

    • Author(s)
      Takahashi H, Asahina R, Kitano T, Yoshihara S and Tsuboi A
    • Organizer
      Keystone Symposia: Neurogenesis during Development and in the Adult Brain
    • Place of Presentation
      Olympic Valley, CA, USA
    • Year and Date
      2017-01-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neural activity-dependent transcription factor Npas4 plays a crucial role in neuronal protection and survival after ischemic stroke2017

    • Author(s)
      Tsuboi A, Asahina R, Yoshihara S, Fujioka M and Takahashi H
    • Organizer
      Cortical Development Conference: Neural Stem Cells to Neural Circuits
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neural activity-dependent transcription factor Npas4 is required for neuroprotection and survival after stroke2017

    • Author(s)
      Takahashi H, Asahina R, Yoshihara S and Tsuboi A
    • Organizer
      第40回日本分子生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Neural activity-dependent transcription factor Npas4 is required for neuroprotection and survival after stroke2017

    • Author(s)
      Takahashi H, Asahina R, Yoshihara S, Fujioka M and Tsuboi A
    • Organizer
      第40回日本神経科学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Oncofetal trophoblast glycoprotein 5T4 is involved in the maintenance of mouse taste bud cells2017

    • Author(s)
      高橋弘雄、高橋佑佳、桐田忠昭、坪井昭夫
    • Organizer
      第51回日本味と匂学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Neural activity-induced transcription factor Npas4 is required for neuroprotection and survival after stroke2016

    • Author(s)
      Takahashi H, Asahina R, Kitano T, Yoshihara S and Tsuboi A
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] A specific subtype of newborn olfactory bulb interneurons is required for behaviors on odor detection and discrimination2016

    • Author(s)
      Takahashi H, Yoshihara S, Ogawa Y, Asahina R, Kitano T and Tsuboi A
    • Organizer
      第39回日本神経科学会大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] A specific subtype of olfactory bulb interneurons is necessary for odor detection and odor-background segregation2016

    • Author(s)
      Takahashi H, Yoshihara S, Ogawa Y, Asahina R, Kitano T and Tsuboi A
    • Organizer
      The 17th International Symposium on Olfaction and Taste (ISOT XVII)
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] A specific subtype of olfactory bulb interneurons is necessary for odor detection and odor-background segregation2016

    • Author(s)
      Takahashi H, Yoshihara S, Ogawa Y, Asahina R, Kitano T, Tsuboi A
    • Organizer
      The 17th International Symposium on Olfaction and Taste (ISOT 2016)
    • Place of Presentation
      Yokohama (Japan)
    • Year and Date
      2016-06-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A specific subtype of newborn interneurons in the olfactory bulb is required for behaviors on odor detection and discrimination2016

    • Author(s)
      Takahashi H, Yoshihara S, Ogawa Y, Asahina R, Kinoshita M, Tsuboi A
    • Organizer
      Conference on Neurogenesis 2016: Implications for Lifelong Development and Disease
    • Place of Presentation
      Cancun (Mexico)
    • Year and Date
      2016-03-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A specific subtype of adult-born interneurons in the olfactory bulb is required for behaviors on odor detection and discrimination2015

    • Author(s)
      Tsuboi A, Yoshihara S, Ogawa Y, Asahina R, Kinoshita M, Takahashi H
    • Organizer
      Current Trends in Biomedicine 2015: Development and Adult Neurogenesis in the Central Nervous System
    • Place of Presentation
      Baeza (Spain)
    • Year and Date
      2015-10-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A specific subtype of newborn interneurons in the olfactory bulb play a crucial role in odor detection and discrimination2015

    • Author(s)
      Tsuboi A, Takahashi H, Yoshihara S, Ogawa Y, Stern PL
    • Organizer
      The 2015 Bridging Biomedical Worlds Symposium: From Neural Circuitry to Neurotechnology
    • Place of Presentation
      Tokyo (Japan)
    • Year and Date
      2015-05-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] Electroporation Methods in Neuroscience (Neuromethods)2015

    • Author(s)
      Takahashi H, Yoshihara S, Asahina R, Tamada Y, *Tsuboi A
    • Total Pages
      11
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report
  • [Book] Handbook of Olfaction and Gustation, Third Edition2015

    • Author(s)
      Tsuboi A, Sakano H
    • Total Pages
      10
    • Publisher
      Wiley-Blackwell
    • Related Report
      2015 Research-status Report
  • [Remarks] 脳神経システム医科学HP

    • URL

      http://www.naramed-u.ac.jp/~amrc-lab1/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Remarks] 奈良県立医科大学 > 先端医学研究機構 > 脳神経システム医科学

    • URL

      http://www.naramed-u.ac.jp/university/subject_and_department_j/advanced_medical_research_center/noushinkei.html

    • Related Report
      2016 Research-status Report
  • [Remarks] お知らせ 「においを感じる度合いを調節する神経メカニズムを世界で初めて解明!」

    • URL

      http://www.naramed-u.ac.jp/university/kanrenshisetsu/sangakukan/oshirase.html

    • Related Report
      2016 Research-status Report
  • [Remarks] HOME(脳神経システム医科学)

    • URL

      http://www.naramed-u.ac.jp/~amrc-lab1/

    • Related Report
      2015 Research-status Report

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

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