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Utility of novel compounds with anti-oxidative stress properties as therapeutic agents for schizophrenia

Research Project

Project/Area Number 21K07511
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

UEHARA Takashi  金沢医科大学, 医学部, 教授 (70303229)

Co-Investigator(Kenkyū-buntansha) 片岡 譲  金沢医科大学, 医学部, 助教 (50896892)
鈴木 道雄  富山大学, 学術研究部医学系, 教授 (40236013)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords統合失調症 / 抗酸化ストレス / 認知機能 / 新規治療薬 / プレパルス抑制テスト / メタンフェタミン誘発移所運動量 / 酸化ストレス / モデル動物
Outline of Research at the Start

本研究は、未だ根本的な薬物療法がない統合失調症とその関連疾患に対して、われわれが独自に開発した抗酸化作用を有する新規化合物(特許出願中、特願2019-95359)の治療薬としての効果を、統合失調症のモデル動物を用いて評価するものである。

Outline of Final Research Achievements

We synthesized new chemicals with antioxidant properties as therapeutic agents for schizophrenia. New chemicals were administered to rats transiently exposed to MK-801 (non-competitive NMDA receptor antagonist) in the neonatal period as an animal model of schizophrenia for 14 days around the period of puberty (postnatal days; PD49-56). On PD57-59, novel object recognition test (NORT), pre-pulse inhibition (PPI), and methamphetamine (MAP)-induced locomotor activity were assessed, followed by glutathione (GSH) levels and the number of parvalbumin (PV)-positive GABA neurons in the medial prefrontal cortex (mPFC). Administration of new chemicals improved NORT and PPI abnormalities in animal models and ameliorated MAP-induced hyperlocomotion. In addition, administration of the new chemicals for 14 days reversed the decrease in GSH levels and the reduction in PV-positive neurons in the mPFC in the model rats.

Academic Significance and Societal Importance of the Research Achievements

今今回の結果から、統合失調症のモデル動物において、新規化合物が抗酸化ストレス作用をもち、形態学的変化(PV陽性GABA神経数の減少)を改善した。さらに認知機能改善効果や抗ドーパミン作用を有することが明らかとなった。このことは新規化合物が統合失調症に対する新たな治療薬となる可能性を示すと思われる。特に認知機能障害は統合失調症の予後を左右するが、従来の抗精神病薬では改善が乏しかったことを考慮すると、今回の結果は統合失調症治療薬開発において、抗酸化ストレス作用が新たなアプローチとなることを示せたと考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2022 2021

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Apocynin-tandospirone derivatives suppress methamphetamine-induced hyperlocomotion in rats with neonatal exposure to dizocilpine2022

    • Author(s)
      Uehara T, Kurachi M, Kondo T, Abe H, Itoh H, Sumiyoshi T, Suzuki M
    • Journal Title

      Journal of Personalized Medicine

      Volume: 12 Issue: 3 Pages: 366-366

    • DOI

      10.3390/jpm12030366

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Apocynin-tandospirone derivatives demonstrate antioxidant properties in the animal model of schizophrenia2021

    • Author(s)
      Uehara T, Kurachi M, Kondo T, Abe H, Zhao QL, Sumiyoshi T, Suzuki M
    • Journal Title

      Advances in Redox Research

      Volume: 3 Pages: 100013-100013

    • DOI

      10.1016/j.arres.2021.100013

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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