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Development of hippocampal neurogenesis-promoting drugs as a target for the treatment and prevention of psychiatric disorders

Research Project

Project/Area Number 26460102
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionTohoku Medical and Pharmaceutical University

Principal Investigator

NAKAGAWASAI Osamu  東北医科薬科大学, 薬学部, 准教授 (50296018)

Co-Investigator(Kenkyū-buntansha) 小野木 弘志  東北福祉大学, 健康科学部, 講師 (50610200)
根本 亙  東北医科薬科大学, 薬学部, 助手 (80635136)
Co-Investigator(Renkei-kenkyūsha) TAN-NO Koichi  東北医科薬科大学, 薬学部, 教授 (20207260)
OBARA Yutarou  山形大学, 医学部, 准教授 (40400270)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords神経新生 / 認知症 / うつ病 / 脳由来神経栄養因子 / 動物モデル / うつ / 記憶障害 / 嗅球摘出動物 / 海馬歯状回 / スカブロニン / 嗅球摘出
Outline of Final Research Achievements

The aim of this study was to explore the effects and underlying mechanisms of a newly synthesized scabronine G - methylester (SG-ME) on memory impairment in olfactory bulbectomized (OBX) mice, experimental animal models of depression and dementia. We observed that the memory impairment in OBX mice was improved at 24 hours after an intracerebroventricular (i.c.v.) injection of SG-ME. The present study has shown that SG-ME has anti-dementia effect, and the SG-ME activity to improve impaired memory is accompanied by enhancement of hippocampal cell proliferation mediated via activation of brain-derived neurotrophic factor - extracellular signal-regulated kinase - cAMP-response element binding protein (BDNF-ERK-CREB) signal pathway on neuronal cells. These results indicate that SG-ME may become a potential leading compound for drug development for Alzheimer's disease.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (20 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] McGill University(Canada)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] McGill大学(カナダ)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Alterations in behavioral responses to dopamine agonists in olfactory bulbectomized mice: relationship to changes in the striatal dopaminergic system2016

    • Author(s)
      Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Takeharu Nakajima, Yuichiro Arai, Tadashi Hisamitsu, Koichi Tan-No
    • Journal Title

      Psychopharmacology

      Volume: 233 Issue: 7 Pages: 1311-1322

    • DOI

      10.1007/s00213-016-4224-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] BE360, a new selective estrogen receptor modulator, produces antidepressant and antidementia effects through the enhancement of hippocampal cell proliferation in olfactory bulbectomized mice.2016

    • Author(s)
      Osamu Nakagawasai, Wataru Nemoto, Hiroshi Onogi, Takahiro Moriya, Jia-Rong Lin, Takayo Odaira, Fukie Yaoita, Takumi Ogawa, Kiminori Ohta, Yasuyuki Endo, Koichi Tan-No
    • Journal Title

      Behav Brain Res

      Volume: 297 Pages: 315-322

    • DOI

      10.1016/j.bbr.2015.10.033

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 嗅球摘出マウスの精神機能障害に対する肝臓水解物の効果:海馬AMP活性化プロテインキナーゼの関与について2017

    • Author(s)
      中川西修,山田耕太郎,小平貴代,佐久間若菜,根本亙,櫻井英知,丹野孝一
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 嗅球摘出マウスのうつ様行動に対するメマンチンの効果2017

    • Author(s)
      髙橋浩平,中川西修,根本亙,小平貴代,丹野孝一
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学川内キャンパス(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 嗅球摘出マウスの認知機能障害に対するアリピプラゾールの効果2017

    • Author(s)
      髙橋浩平,中川西修,根本亙,小平貴代,荒井裕一朗,久光正,丹野孝一
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 嗅球摘出マウスのうつ様行動に対するAngiotensin変換酵素阻害薬Captoprilの効果2017

    • Author(s)
      小野涼太郎,中川西修,小平貴代,佐久間若菜,根本亙,丹野孝一
    • Organizer
      第26回神経行動薬理若手研究者の集い
    • Place of Presentation
      福岡大学メディカルホール(福岡県福岡市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 精神疾患モデル動物作製とその発現機序の解明2016

    • Author(s)
      中川西 修
    • Organizer
      生体機能と創薬シンポジウム2016
    • Place of Presentation
      東北大学川内キャンパス(宮城県仙台市)
    • Year and Date
      2016-08-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 更年期障害モデルマウスのうつ状態に対する新規選択的エストロゲン受容体モジュレターBE360の効果2016

    • Author(s)
      佐久間若菜,中川西修,根本亙,八百板富紀枝,小川卓巳,太田公規,遠藤泰之,丹野孝一
    • Organizer
      生体機能と創薬シンポジウム2016
    • Place of Presentation
      東北大学川内キャンパス(宮城県仙台市)
    • Year and Date
      2016-08-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] うつ病モデルマウスの脳内ドパミン神経機能変化について2016

    • Author(s)
      中川西修,髙橋浩平,根本亙,菊地恵理,佐久間若菜,小平貴代,八百板富紀枝,荒井裕一朗,只野武,丹野孝一
    • Organizer
      第20回活性アミンに関するワークショップ
    • Place of Presentation
      ホテルマークワンつくば研究学園(茨城県つくば市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] スカブロニンG-メチルエステルの認知障害改善作用とその機序について2016

    • Author(s)
      小平貴代,中川西修,林嘉蓉,根本亙,佐久間若菜,小原祐太郎,小早川優,中田雅久,丹野孝一
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2016
    • Place of Presentation
      東北大学川内キャンパス(宮城県仙台市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 嗅球摘出マウスにおける線条体Dopamine受容体機能変化とそれに及ぼす抗うつ薬の影響2016

    • Author(s)
      髙橋浩平,中川西修,根本亙,菊地恵理,佐久間若菜,小平貴代,丹野孝一
    • Organizer
      第67回日本薬理学会北部会
    • Place of Presentation
      北海道大学学術交流会館(北海道札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 林嘉蓉、中川西修、根本亙、小原祐太郎、八百板富紀枝、荒井裕一朗、只野武、小早川優、中田雅久、丹野孝一2015

    • Author(s)
      スカブロニンG メチルエステルは認知障害やうつ様症状を海馬の神経新生促進作用により改善する
    • Organizer
      第19回活性アミンに関するワークショップ
    • Place of Presentation
      小名浜オーシャンホテル、LATOV (福島県いわき市)
    • Year and Date
      2015-08-20
    • Related Report
      2015 Research-status Report
  • [Presentation] The effects of liver hydrolysate on physical fatigue and sickness behavior2015

    • Author(s)
      Kotaro Yamada, Osamu Nakagawasai, Wataru Nemoto, Hidetomo Sakurai, Koichi Tan-No
    • Organizer
      12th Asian Congress of Nutrition
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2015-05-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Scabronine G-methylester attenuates hippocampal neurogenesis impairment and the memory deficits induced by olfactory bulbectomy2015

    • Author(s)
      Jia Rong Lin, Osamu Nakagawasai, Wataru Nemoto, Yutaro Obara, Fukie Yaoita, Yu Kobayakawa, Masahisa Nakada, Koichi Tan-No
    • Organizer
      第24回神経行動薬理若手研究者の集い
    • Place of Presentation
      名古屋、愛知県
    • Year and Date
      2015-03-17
    • Related Report
      2014 Research-status Report
  • [Presentation] メチルアゾキシメタノールを用いた統合失調症モデルマウスの作製2014

    • Author(s)
      中川西修、手塚大介、根本亙、八百板富紀枝、只野武、丹野孝一
    • Organizer
      第16回応用薬理シンポジウム
    • Place of Presentation
      松島、宮城県
    • Year and Date
      2014-12-05 – 2014-12-06
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] NMDA受容体遮断薬MK-801誘発性記憶障害に対する緑茶成分テアニンの改善効果2014

    • Author(s)
      宮昂平、中川西修、根本亙、八百板富紀枝、丹野孝一
    • Organizer
      宮城薬剤師学術フォーラム2014
    • Place of Presentation
      仙台、宮城県
    • Year and Date
      2014-11-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 胎生期メチルアゾキシメタノール処理マウスが神経発達障害仮説に基づいた統合失調症モデルに成り得るか?2014

    • Author(s)
      中川西修、手塚大介、根本亙、八百板富紀枝、荒井裕一朗、只野武、丹野孝一
    • Organizer
      第18回活性アミンに関するワークショップ
    • Place of Presentation
      高松、香川県
    • Year and Date
      2014-08-30
    • Related Report
      2014 Research-status Report
  • [Presentation] Angiotensin II type 1 receptor-mediated increase in spinal p38 MAPK phosphorylation leads to the induction of nociceptive behavior in mice2014

    • Author(s)
      Osamu Nakagawasai, Wataru Nemoto, Yoshiki Ogata, Fukie Yaoita, Takeshi Tadano, Koichi Tan-No
    • Organizer
      International Narcotics Research Conference 2014
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2014-07-13 – 2014-07-18
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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