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Drug discovery and neurochemical researches about T-type calcium channel in neurogenesis.

Research Project

Project/Area Number 17K15456
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pharmacology in pharmacy
Research InstitutionTohoku University

Principal Investigator

Yabuki Yasushi  東北大学, 薬学研究科, 助教 (70756121)

Research Collaborator Xu Jing  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsT 型カルシウムチャネル / 神経新生 / 海馬神経新生 / 神経薬理学 / うつ様行動 / 薬理学 / 生理学 / 脳・神経、脳神経疾患
Outline of Final Research Achievements

Number of depressive patients is over million in Japan, and it is serious social problem that depressive patients may account for 60% of suicides. We succeeded to develop T-type calcium channel enhancer. This compound improved depressive-like behaviors in olfactory-bulbectomized (OBX) mice. Whereas depressive-like behaviors are closely associated with hippocampal adult neurogenesis, T-type calcium channel enhancer could restore impaired hippocampal neurogenesis in OBX mice. In addition, T-type calcium channel enhancer enhanced monoamine releases in the mouse hippocampus, which have important role in depression. Finally, we observed impaired neurogenesis in the T-type calcium channel gene knock out mouse hippocampus. Taken together, we suggest that T-type calcium channel may have an important role in adult neurogenesis and brain homeostasis.

Academic Significance and Societal Importance of the Research Achievements

既存の抗うつ薬はモノアミントランスポーターを阻害し、セロトニンやノルアドレナリンなどのモノアミンを増加させることで抗うつ効果を示す。しかしながら、抗うつ効果が得られるまでに時間がかかること、治療抵抗性うつ病患者の増加していることから新規作用機序の治療薬開発が求められている。また、T 型カルシウムチャネル賦活化薬の開発は世界初であり、研究のオリジナル性および独創性は極めて高いと考えられる。さらに、T 型カルシウムチャネルの脳高次機能については未だ不明な点が多く、神経新生やうつ病との関連が明らかになれば神経科学の発展と新規抗うつ薬の開発に大きく貢献できると考えられる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] T-type calcium channel enhancer SAK3 promotes dopamine and serotonin releases in the hippocampus in naive and amyloid precursor protein knock-in mice.2018

    • Author(s)
      Wang S, Yabuki Y, Matsuo K, Xu J, Izumi H, Sakimura K, Saito T, Saido TC, Fukunaga K.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 12 Pages: e0206986-e0206986

    • DOI

      10.1371/journal.pone.0206986

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] T-type calcium channel enhancer SAK3 produces anti-depressant-like effects by promoting adult hippocampal neurogenesis in olfactory bulbectomized mice2018

    • Author(s)
      Xu Jing、Yabuki Yasushi、Yu Mengze、Fukunaga Kohji
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 137 Issue: 4 Pages: 333-341

    • DOI

      10.1016/j.jphs.2018.07.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Disease-modifying Drug Candidate, SAK3 Improves Cognitive Impairment and Inhibits Amyloid beta Deposition in App Knock-in Mice.2018

    • Author(s)
      Izumi H, Shinoda Y, Saito T, Saido TC, Sato K, Yabuki Y, Matsumoto Y, Kanemitsu Y, Tomioka Y, Abolhassani N, Nakabeppu Y, Fukunaga K.
    • Journal Title

      Neuroscience.

      Volume: 377 Pages: 87-97

    • DOI

      10.1016/j.neuroscience.2018.02.031

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling.2018

    • Author(s)
      Husain N, Yabuki Y, Shinoda Y, Fukunaga K.
    • Journal Title

      Pharmacology.

      Volume: 101 Issue: 5-6 Pages: 309-321

    • DOI

      10.1159/000488083

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The T-type calcium channel enhancer SAK3 inhibits neuronal death following transient brain ischemia via nicotinic acetylcholine receptor stimulation.2017

    • Author(s)
      Yabuki Y, Jing X, Fukunaga K.
    • Journal Title

      Neurochem Int.

      Volume: 108 Pages: 272-281

    • DOI

      10.1016/j.neuint.2017.04.015

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 脳における T 型カルシウムチャネル機能の解明を目指して2017

    • Author(s)
      矢吹 悌、松尾 和哉、若森 実、福永 浩司
    • Organizer
      第18回ブレインサイエンス研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] T 型カルシウムチャネル賦活薬 SAK3 による神経新生促進作用2017

    • Author(s)
      于 梦澤、許 晶、矢吹 悌、福永 浩司
    • Organizer
      第68回 日本薬理学会北部会
    • Related Report
      2017 Research-status Report
  • [Presentation] T 型カルシウムチャネルの神経薬理学的研究2017

    • Author(s)
      矢吹 悌、福永 浩司
    • Organizer
      生体機能と創薬シンポジウム2017
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2020-03-30  

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