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Pathomechanisms of neuropsychiatric disorders associated with tripartite synaptic transmission

Research Project

Project/Area Number 19K08073
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionMie University

Principal Investigator

Okada Motohiro  三重大学, 医学系研究科, 教授 (10281916)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords認知機能 / 情報伝達 / 神経 / グリア / 病態生理 / アストロサイト / 自閉症 / 情動安定化 / ADHD / てんかん / グルタミン酸 / 認知 / 三者間伝達
Outline of Research at the Start

精神医学は、病態生理仮説に基づき、多くの精神障害に対し、神経伝達機能補正を介した治療法を構築し成果を上げてきた。従来の病態生理仮説では十分に対処できない亜型に対し、新たな介入方法を開発するために、神経伝達に分極グリア伝達機能変異を加えた、新たな三者間伝達仮説構築を試みる。
1)グリア伝達物質の開口分泌機構。2)抗精神病薬・抗うつ薬・抗てんかん薬のグリア伝達に対する作用解析。3)分極アストロサイトと炎症性サイトカインのグリア伝達に与える影響解析。4)中枢神経系ホメオスタシス制御を担う、イオンチャネルとトランスポーターのグリア伝達に与える影響の解析。

Outline of Final Research Achievements

Mediodorsal thalamic nucleus receives monoaminergic projections from midbrain and also various sensory inputs.
The improvement of input efficiency and/or output efficiency of the thalamocortical transmission contributed to regulation of cognitive integration and improvement of executive function. Neurotransmission played important roles in the regulation of transmission in milliseconds orders, but glial transmission in regulated that in several day orders. Connexin, which expresses in astrocytes, also provided the regulation mechanisms of long-term astroglial transmissions.

Academic Significance and Societal Importance of the Research Achievements

認知機能の中で、知覚統合と遂行機能は少なくとも短期的機能制御機構は神経伝達が担っているが、これらの長期的な制御には、グリア伝達が制御を担っており、神経とグリアの情報伝達としてのtripartite synaptic transmissionが、認知機能制御に重要な役割を果たしている可能性を示すことが出来た。この知見は、従来の診断分類に従った病態解明研究ではなく、機能的な障害による障害分類に基づいた病態生理解析に有用性を示すものである。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2022 2021 2020 2019

All Journal Article (23 results) (of which Peer Reviewed: 17 results,  Open Access: 17 results)

  • [Journal Article] High frequency oscillations play important roles in development of epileptogenesis/ictogenesis via activation of astroglial signallings2022

    • Author(s)
      Fukuyama Kouji、Okada Motohiro
    • Journal Title

      Biomedicine and Pharmacotherapy

      Volume: 149 Pages: 112846-112846

    • DOI

      10.1016/j.biopha.2022.112846

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of 5-HT7 receptor inverse agonism of lurasidone on monoaminergic tripartite synaptic transmission and pathophysiology of lower risk of weight gain2022

    • Author(s)
      Fukuyama Kouji、Motomura Eishi、Shiroyama Takashi、Okada Motohiro
    • Journal Title

      Biomedicine and Pharmacotherapy

      Volume: 148 Pages: 112750-112750

    • DOI

      10.1016/j.biopha.2022.112750

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of an Atypical Antipsychotic, Zotepine, on Astroglial L-Glutamate Release through Hemichannels: Exploring the Mechanism of Mood-Stabilising Antipsychotic Actions and Antipsychotic-Induced Convulsion2021

    • Author(s)
      Fukuyama Kouji、Okada Motohiro
    • Journal Title

      Pharmaceuticals

      Volume: 14 Issue: 11 Pages: 1116-1116

    • DOI

      10.3390/ph14111116

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct Effects of Escitalopram and Vortioxetine on Astroglial L-Glutamate Release Associated with Connexin432021

    • Author(s)
      Shiroyama Takashi、Fukuyama Kouji、Okada Motohiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 18 Pages: 10013-10013

    • DOI

      10.3390/ijms221810013

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin432021

    • Author(s)
      Fukuyama Kouji、Okada Motohiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 11 Pages: 5623-5623

    • DOI

      10.3390/ijms22115623

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic Administrations of Guanfacine on Mesocortical Catecholaminergic and Thalamocortical Glutamatergic Transmissions2021

    • Author(s)
      Fukuyama Kouji、Nakano Tomosuke、Shiroyama Takashi、Okada Motohiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 8 Pages: 4122-4122

    • DOI

      10.3390/ijms22084122

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brivaracetam prevents astroglial l-glutamate release associated with hemichannel through modulation of synaptic vesicle protein2021

    • Author(s)
      Okada Motohiro、Fukuyama Kouji、Shiroyama Takashi、Ueda Yuto
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 138 Pages: 111462-111462

    • DOI

      10.1016/j.biopha.2021.111462

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Can rodent models manifest pathomechanisms of genetic epilepsy?2021

    • Author(s)
      Okada Motohiro
    • Journal Title

      British Journal of Pharmacology

      Volume: in press Issue: 8 Pages: 1620-1639

    • DOI

      10.1111/bph.15443

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current Limitations and Candidate Potential of 5-HT7 Receptor Antagonism in Psychiatric Pharmacotherapy2021

    • Author(s)
      Okubo Ruri、Hasegawa Toshiki、Fukuyama Kouji、Shiroyama Takashi、Okada Motohiro
    • Journal Title

      Frontiers in Psychiatry

      Volume: 12 Pages: 623684-623684

    • DOI

      10.3389/fpsyt.2021.623684

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Astroglial Connexin43 as a Potential Target for a Mood Stabiliser2020

    • Author(s)
      Okada Motohiro、Oka Tomoka、Nakamoto Misaki、Fukuyama Kouji、Shiroyama Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 1 Pages: 339-339

    • DOI

      10.3390/ijms22010339

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age-Dependent and Sleep/Seizure-Induced Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy2020

    • Author(s)
      Fukuyama Kouji、Okada Motohiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 21 Pages: 8142-8142

    • DOI

      10.3390/ijms21218142

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Candidate Strategies for Development of a Rapid-Acting Antidepressant Class That Does Not Result in Neuropsychiatric Adverse Effects: Prevention of Ketamine-Induced Neuropsychiatric Adverse Reactions2020

    • Author(s)
      Okada Motohiro、Kawano Yasuhiro、Fukuyama Kouji、Motomura Eishi、Shiroyama Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 21 Pages: 7951-7951

    • DOI

      10.3390/ijms21217951

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin432020

    • Author(s)
      Okada Motohiro、Fukuyama Kouji、Shiroyama Takashi、Murata Masahiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 19 Pages: 7019-7019

    • DOI

      10.3390/ijms21197019

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interaction between Mesocortical and Mesothalamic Catecholaminergic Transmissions Associated with NMDA Receptor in the Locus Coeruleus2020

    • Author(s)
      Okada Motohiro、Fukuyama Kouji
    • Journal Title

      Biomolecules

      Volume: 10 Issue: 7 Pages: 990-990

    • DOI

      10.3390/biom10070990

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Carbamazepine, Lacosamide and Zonisamide on Gliotransmitter Release Associated with Activated Astroglial Hemichannels2020

    • Author(s)
      Fukuyama Kouji、Ueda Yuto、Okada Motohiro
    • Journal Title

      Pharmaceuticals

      Volume: 13 Issue: 6 Pages: 117-117

    • DOI

      10.3390/ph13060117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulated and Hyperactivated Thalamic Connexin 43 Plays Important Roles in Pathomechanisms of Cognitive Impairment and Seizure of Autosomal Dominant Sleep-Related Hypermotor Epilepsy with S284L-Mutant α4 Subunit of Nicotinic ACh Receptor2020

    • Author(s)
      Fukuyama Kouji、Fukuzawa Masashi、Okada Motohiro
    • Journal Title

      Pharmaceuticals

      Volume: 13 Issue: 5 Pages: 99-99

    • DOI

      10.3390/ph13050099

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulated Connexin 43 Induced by Loss-of-Functional S284L-Mutant α4 Subunit of Nicotinic ACh Receptor Contributes to Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy2020

    • Author(s)
      Fukuyama Kouji、Fukuzawa Masashi、Okubo Ruri、Okada Motohiro
    • Journal Title

      Pharmaceuticals

      Volume: 13 Issue: 4 Pages: 58-58

    • DOI

      10.3390/ph13040058

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathomechanism of nocturnal paroxysmal dystonia in autosomal dominant sleep-related hypermotor epilepsy with S284L-mutant α4 subunit of nicotinic ACh receptor2020

    • Author(s)
      Fukuyama Kouji、Fukuzawa Masashi、Shiroyama Takashi、Okada Motohiro
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 126 Pages: 110070-110070

    • DOI

      10.1016/j.biopha.2020.110070

    • Related Report
      2019 Research-status Report
  • [Journal Article] Activation of Astroglial Connexin Is Involved in Concentration-Dependent Double-Edged Sword Clinical Action of Clozapine2020

    • Author(s)
      Fukuyama Kouji、Okubo Ruri、Murata Masahiko、Shiroyama Takashi、Okada Motohiro
    • Journal Title

      Cells

      Volume: 9 Issue: 2 Pages: 414-414

    • DOI

      10.3390/cells9020414

    • Related Report
      2019 Research-status Report
  • [Journal Article] Pathogenesis and pathophysiology of autosomal dominant sleep‐related hypermotor epilepsy with S284L‐mutant α4 subunit of nicotinic ACh receptor2020

    • Author(s)
      Fukuyama Kouji、Fukuzawa Masashi、Shiroyama Takashi、Okada Motohiro
    • Journal Title

      British Journal of Pharmacology

      Volume: - Issue: 9 Pages: 2143-2162

    • DOI

      10.1111/bph.14974

    • Related Report
      2019 Research-status Report
  • [Journal Article] Can Financial Support Reduce Suicide Mortality Rates?2019

    • Author(s)
      Kato Ryo、Okada Motohiro
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 16 Issue: 23 Pages: 4797-4797

    • DOI

      10.3390/ijerph16234797

    • Related Report
      2019 Research-status Report
  • [Journal Article] Lurasidone Sub-Chronically Activates Serotonergic Transmission via Desensitization of 5-HT1A and 5-HT7 Receptors in Dorsal Raphe Nucleus2019

    • Author(s)
      Okada、Fukuyama、Okubo、Shiroyama、Ueda
    • Journal Title

      Pharmaceuticals

      Volume: 12 Issue: 4 Pages: 149-149

    • DOI

      10.3390/ph12040149

    • Related Report
      2019 Research-status Report
  • [Journal Article] Lurasidone inhibits NMDA receptor antagonist‐induced functional abnormality of thalamocortical glutamatergic transmission via 5‐HT 7 receptor blockade2019

    • Author(s)
      Okada Motohiro、Fukuyama Kouji、Ueda Yuto
    • Journal Title

      British Journal of Pharmacology

      Volume: 176 Issue: 20 Pages: 4002-4018

    • DOI

      10.1111/bph.14804

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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