• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of brain angiotensin system on animal model of depression

Research Project

Project/Area Number 18K06687
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
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) 大河原 雄一  東北医科薬科大学, 薬学部, 教授 (40333801)
小野木 弘志  東北福祉大学, 健康科学部, 准教授 (50610200)
根本 亙  東北医科薬科大学, 薬学部, 助教 (80635136)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsアンジオテンシン / うつ病 / 神経新生 / カプトプリル / Ang(1-7) / BDNF / Mas受容体 / アンジオテンシン系 / Ang (1-7)
Outline of Final Research Achievements

Olfactory bulbectomized (OBX) mice shows neurochemical and behavioral changes similar to those observed in individuals with depressive disorders. Intraperitoneal administration of Captopril (CAP) for one week showed antidepressant-like effects in OBX mice. Previous study revealed that CAP treatment increased angiotensin (1-7) [Ang (1-7)] levels in rat brain. OBX mice showed reduced hippocampal Ang (1-7), Brain-derived neurotrophic factor (BDNF) levels and neurogenesis. Interestingly, these changes were reversed by CAP administration. Further, antidepressant-like effect of CAP was abolished by the co-administration of an antagonist for Ang (1-7) receptor MAS. These results suggest that CAP-induced antidepressant-like effects may be associated with enhanced hippocampal neurogenesis via Ang (1-7) / MAS signaling pathway.

Academic Significance and Societal Importance of the Research Achievements

これまで血圧などの循環器系にAngiotensin (Ang)系が関与していることが分かっていたが、今回の研究により脳内のAng系がうつ病にも関与するという新たな機能的役割を見出した。さらに、うつ病動物モデルに対し高血圧の治療に用いられている既存のAng変換酵素阻害薬(ACE阻害薬)であるカプトプリル(一般名)が抗うつ作用を有することを発見した。これらのことから、ACE阻害薬は循環器系疾患のみならず、既存の抗うつ薬よりも副作用が軽度な抗うつ薬として新規適応拡大(エコファーマ)の可能性が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

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

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] McGill University(カナダ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] McGill大学(カナダ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] A novel dipeptide derived from porcine liver hydrolysate induces recovery from physical fatigue in a mouse model2021

    • Author(s)
      Nakagawasai Osamu、Yamada Kotaro、Sakuma Wakana、Takahashi Kohei、Odaira Takayo、Yamagata Ryota、Nemoto Wataru、Ejima Akika、Sato Kenji、Tan-No Koichi
    • Journal Title

      Journal of Functional Foods

      Volume: 76 Pages: 104312-104312

    • DOI

      10.1016/j.jff.2020.104312

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver hydrolysate improves depressive-like behavior in olfactory bulbectomized mice: Involvement of hippocampal neurogenesis through the AMPK/BDNF/CREB pathway2020

    • Author(s)
      Nakagawasai Osamu, Yamada Kotaro, Odaira Takayo, Takahashi Kohei, Nemoto Wataru, Sakuma Wakana, Wakou Miharu, Lin Jia-Rong, Tan-No Koichi
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 143 Issue: 1 Pages: 52-55

    • DOI

      10.1016/j.jphs.2020.01.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Liver hydrolysate prevents depressive-like behavior in an animal model of colitis: Involvement of hippocampal neurogenesis via the AMPK/BDNF pathway2020

    • Author(s)
      Nakagawasai Osamu、Yamada Kotaro、Takahashi Kohei、Odaira Takayo、Sakuma Wakana、Ishizawa Daisuke、Takahashi Naruya、Onuma Kentaro、Hozumi Chikako、Nemoto Wataru、Tan-No Koichi
    • Journal Title

      Behavioural Brain Research

      Volume: 390 Pages: 112640-112640

    • DOI

      10.1016/j.bbr.2020.112640

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antidepressant effect of BE360, a new selective estrogen receptor modulator, activated via CREB/BDNF, Bcl-2 signaling pathways in ovariectomized mice2020

    • Author(s)
      Sakuma Wakana、Nakagawasai Osamu、Nemoto Wataru、Odaira Takayo、Ogawa Takumi、Ohta Kiminori、Endo Yasuyuki、Tan-No Koichi
    • Journal Title

      Behavioural Brain Research

      Volume: 393 Pages: 112764-112764

    • DOI

      10.1016/j.bbr.2020.112764

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dopamine D2 receptor supersensitivity in the hypothalamus of olfactory bulbectomized mice2020

    • Author(s)
      Takahashi Kohei、Nakagawasai Osamu、Nakajima Takeharu、Okubo Myu、Nishimura Yuki、Sakuma Wakana、Yamagata Ryota、Nemoto Wataru、Miyagawa Kazuya、Kurokawa Kazuhiro、Mochida-Saito Atsumi、Tsuji Minoru、Takeda Hiroshi、Tadano Takeshi、Tan-No Koichi
    • Journal Title

      Brain Research

      Volume: 1746 Pages: 147015-147015

    • DOI

      10.1016/j.brainres.2020.147015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Scabronine G Methyl Ester Improves Memory-Related Behavior and Enhances Hippocampal Cell Proliferation and Long-Term Potentiation via the BDNF-CREB Pathway in Olfactory Bulbectomized Mice2020

    • Author(s)
      Nakagawasai Osamu、Lin Jia-Rong、Odaira Takayo、Takahashi Kohei、Nemoto Wataru、Moriguchi Shigeki、Yabuki Yasushi、Kobayakawa Yu、Fukunaga Kohji、Nakada Masahisa、Tan-No Koichi
    • Journal Title

      Frontiers in Pharmacology

      Volume: 11 Pages: 583291-583291

    • DOI

      10.3389/fphar.2020.583291

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of prefrontal cortical 5-HT2A receptors and serotonin transporter in the behavioral deficits in post-pubertal rats following neonatal lesion of the ventral hippocampus2020

    • Author(s)
      Mitazaki Satoru、Nakagawasai Osamu、Onogi Hiroshi、Watanabe Kenya、Takahashi Kohei、Tan-No Koichi、Quirion R?mi、Srivastava Lalit K、Tadano Takeshi
    • Journal Title

      Behavioural Brain Research

      Volume: 377 Pages: 112226-112226

    • DOI

      10.1016/j.bbr.2019.112226

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prenatal treatment with methylazoxymethanol acetate as a neurodevelopmental disruption model of schizophrenia in mice2019

    • Author(s)
      Takahashi Kohei、Nakagawasai Osamu、Sakuma Wakana、Nemoto Wataru、Odaira Takayo、Lin Jia-Rong、Onogi Hiroshi、Srivastava Lalit K.、Tan-No Koichi
    • Journal Title

      Neuropharmacology

      Volume: 150 Pages: 1-14

    • DOI

      10.1016/j.neuropharm.2019.02.034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanisms underpinning AMP-activated protein kinase-related effects on behavior and hippocampal neurogenesis in an animal model of depression2019

    • Author(s)
      Odaira Takayo、Nakagawasai Osamu、Takahashi Kohei、Nemoto Wataru、Sakuma Wakana、Lin Jia-Rong、Tan-No Koichi
    • Journal Title

      Neuropharmacology

      Volume: 150 Pages: 121-133

    • DOI

      10.1016/j.neuropharm.2019.03.026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain?gut axis2019

    • Author(s)
      Takahashi Kohei、Nakagawasai Osamu、Nemoto Wataru、Odaira Takayo、Sakuma Wakana、Onogi Hiroshi、Nishijima Hiroaki、Furihata Ryuji、Nemoto Yukio、Iwasa Hiroyuki、Tan-No Koichi、Tadano Takeshi
    • Journal Title

      Journal of Neuroinflammation

      Volume: 16 Issue: 1 Pages: 201-201

    • DOI

      10.1186/s12974-019-1580-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 嗅球摘出マウスにおけるcaptoprilの海馬アンジオテンシン (1-7) / MAS1経路を介した抗うつ様効果2021

    • Author(s)
      若生 美春、中川西 修、小山 泰成、小平 貴代、佐久間 若菜、山縣 涼太、根本 亙、丹野 孝一
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Behavioral, cytoarchitectural, and neurochemical changes in the offspring of methylazoxymethanol treated in mice2019

    • Author(s)
      Osamu Nakagawasai, Kohei Takahashi, Wakana Sakuma, Wataru Nemoto, Takayo Odaira, Lin Jia-Rong, Hiroshi Onogi, Lalit K Srivastava, Koichi Tan-No
    • Organizer
      2019 International Society for Neurochemistry Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] p-Hydroxyamphetamine causes prepulse inhibition disruptions in mice: Contribution of catecholamine and serotonin neurotransmission2019

    • Author(s)
      Hiroshi Onogi, Osamu Nakagawasai, Wataru Nemoto, Satoru Mitazaki, Koichi Tan-No, Takeshi Tadano
    • Organizer
      2019 International Society for Neurochemistry Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Angiotensin変換酵素阻害薬Captoprilの抗うつ作用はAngiotensin (1-7)/Mas受容体を介する2019

    • Author(s)
      小平 貴代,中川西 修,小野涼太郎,根本 亙,髙橋 浩平,佐久間若菜,荒井裕一朗,只野 武,丹野 孝一
    • Organizer
      第23回活性アミンに関するワークショップ
    • Related Report
      2019 Research-status Report
  • [Presentation] Captoprilの海馬Angiotensin(1-7)/Mas受容体系の活性化を介した抗うつ効果2019

    • Author(s)
      小平 貴代,中川西 修,小野涼太郎,根本 亙,髙橋 浩平,佐久間若菜,丹野 孝一
    • Organizer
      第58回日本薬学会東北支部大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 海馬AMPKシグナリングの活性化は嗅球摘出マウスのうつ様行動を改善する2019

    • Author(s)
      小平 貴代,中川西 修,根本 亙,髙橋 浩平,佐久間 若菜,丹野 孝一
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] メマンチンの海馬ドパミン神経系を介した抗うつ効果2018

    • Author(s)
      髙橋 浩平,中川西 修,根本 亙,小平 貴代,佐久間若菜,荒井裕一朗,只野 武,丹野 孝一
    • Organizer
      第22回活性アミンに関するワークショップ
    • Related Report
      2018 Research-status Report
  • [Presentation] Memantine produces antidepressant effect through the enhancement of hippocampal neurogenesis in olfactory bulbectomized mice2018

    • Author(s)
      Osamu Nakagawasai, Kohei Takahashi, Wataru Nemoto, Takayo Odaira, Wakana Sakuma, Yuichiro Arai, Takeshi Tadano, Koichi Tan-No
    • Organizer
      31th European College of Neuropsychopharmacology Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 東北医科薬科大学薬学部薬理学教室

    • URL

      https://www.tohoku-mpu.ac.jp/pharmacy/lab/lp_c01/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東北医科薬科大学薬学部薬理学教室

    • URL

      http://www.tohoku-mpu.ac.jp/laboratory/yakuri/index.html

    • Related Report
      2019 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi