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Development of the integrated therapeutic strategy aiming toward drug discovery and pharmacotherapy for treatment-resistant schizophrenia

Research Project

Project/Area Number 20H03392
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionHiroshima University

Principal Investigator

Ago Yukio  広島大学, 医系科学研究科(歯), 教授 (50403027)

Co-Investigator(Kenkyū-buntansha) 中澤 敬信  東京農業大学, 生命科学部, 教授 (00447335)
近藤 昌夫  大阪大学, 大学院薬学研究科, 教授 (50309697)
鈴木 亮  帝京大学, 薬学部, 教授 (90384784)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2023: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2022: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords統合失調症 / コピー数変異 / VIPR2 / iPS細胞 / 遺伝子改変マウス / アンタゴニスト / ペプチド / ドラッグデリバリーシステム
Outline of Research at the Start

本研究では、統合失調症の確度の高い遺伝的要因としてのコピー数変異に着目し、7q36.3微細重複によるVPAC2受容体過剰活性化の病態生理学的意義の解明と、難治性統合失調症の克服に向けた新しい治療技術・創薬戦略の基盤構築を目指す。具体的には、①患者由来細胞とマウスモデルを用いた病態神経基盤の解明と創薬モデルとしての妥当性検証、②生理活性物質等の脳内(部位特異的)送達技術の開発を行う。

Outline of Final Research Achievements

Rare copy number variants (CNVs) have a prominent role in the etiology of schizophrenia and duplications of the VIPR2 gene confer significant risk for schizophrenia. VIPR2 encodes the VPAC2 receptor, which binds to two homologous neuropeptides, PACAP and VIP. In this study, we generated induced pluripotent stem cells from a patient with microduplication of 7q36.3 locus including VIPR2 gene. Under PACAP or VIP treatment condition, neurospheres from patient-derived neural stem cells (NSCs) were smaller than those from control NSCs, suggesting impaired proliferation. We also developed a bacterial artificial chromosome (BAC) transgenic mouse model of VIPR2 CNV that recapitulates the genetic architecture of the susceptibility allele. VIPR2-BAC transgenic mice showed social interaction deficits and cognitive impairment. Finally, we developed a bicyclic peptide KS-133, which shows VIPR2 antagonist activity in vivo and improves cognitive dysfunction in a mouse model of schizophrenia.

Academic Significance and Societal Importance of the Research Achievements

近年、精神疾患は、患者数の増大とともに、自殺や就学・就労困難など社会的な機能の低下を引き起こすなど、大きな社会的損失をもたらす重要疾患であるとの認識が高まっている。本研究では、VIPR2遺伝子重複を有する統合失調症を具体例として、疾患に強く関連する病態とそのメカニズムをヒトとマウス間で双方向性に解析・補完しながら解明し、またVIPR2を選択的に阻害するペプチドを創製した。今後、本ペプチドの有効性の範囲や安全性を確かめ、また脳への移行性をより高める製剤化などを検討しながら臨床研究へと展開していくことで、新しい治療薬の開発につながると期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (97 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (4 results) Journal Article (23 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 21 results,  Open Access: 14 results) Presentation (66 results) (of which Int'l Joint Research: 15 results,  Invited: 13 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] University of California Los Angeles(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of California Los Angeles(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of California Los Angeles(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of California Los Angeles(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Long-lasting anti-despair and anti-anhedonia effects of (S)-norketamine in social isolation-reared mice2024

    • Author(s)
      Yokoyama Rei、Higuchi Momoko、Tanabe Wataru、Tsukada Shinji、Igarashi Hisato、Seiriki Kaoru、Nakazawa Takanobu、Kasai Atsushi、Ago Yukio、Hashimoto Hitoshi
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 154 Issue: 2 Pages: 72-76

    • DOI

      10.1016/j.jphs.2023.12.005

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells2024

    • Author(s)
      Asano Satoshi、Ono Ami、Baba Kaede、Uehara Teru、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Yanamoto Souichi、Tanimoto Kotaro、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 154 Issue: 3 Pages: 139-147

    • DOI

      10.1016/j.jphs.2024.01.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] (R)-ketamine restores anterior insular cortex activity and cognitive deficits in social isolation-reared mice2024

    • Author(s)
      Yokoyama Rei、Ago Yukio、Igarashi Hisato、Higuchi Momoko、Tanuma Masato、Shimazaki Yuto、Kawai Takafumi、Seiriki Kaoru、Hayashida Misuzu、Yamaguchi Shun、Tanaka Hirokazu、Nakazawa Takanobu、Okamura Yasushi、Hashimoto Kenji、Kasai Atsushi、Hashimoto Hitoshi
    • Journal Title

      Molecular Psychiatry

      Volume: - Issue: 5 Pages: 1-11

    • DOI

      10.1038/s41380-024-02419-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of the vasoactive intestinal peptide receptor 2 (VIPR2) antagonist peptide for the treatment of schizophrenia2023

    • Author(s)
      Ago Yukio、Asano Satoshi、Sakamoto Kotaro
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 158 Issue: 3 Pages: 242-245

    • DOI

      10.1254/fpj.22146

    • ISSN
      0015-5691, 1347-8397
    • Year and Date
      2023-05-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressive effect of black tea polyphenol theaflavins in a mouse model of ovalbumin-induced food allergy2023

    • Author(s)
      Ishimoto K, Konishi Y, Otani S, Maeda S, Ago Y, Hino N, Suzuki M, Nakagawa S.
    • Journal Title

      J Nat Med.

      Volume: in press Issue: 3 Pages: 604-609

    • DOI

      10.1007/s11418-023-01686-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The VIPR2-selective antagonist KS-133 changes macrophage polarization and exerts potent anti-tumor effects as a single agent and in combination with an anti-PD-1 antibody2023

    • Author(s)
      Sakamoto K, Kittikulsuth W, Miyako E, Steeve A, Ishimura R, Nakagawa S, Ago Y, Nishiyama A
    • Journal Title

      PLoS One

      Volume: 18 Issue: 7 Pages: e0286651-e0286651

    • DOI

      10.1371/journal.pone.0286651

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of the monoaminergic system in the antidepressant effects of ketamine and its metabolites2023

    • Author(s)
      Ago Y, Yokoyama R, Asano S, Hashimoto H
    • Journal Title

      Neuropharmacology

      Volume: 223 Pages: 109313-109313

    • DOI

      10.1016/j.neuropharm.2022.109313

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vasoactive intestinal peptide receptor 2 signaling promotes breast cancer cell proliferation by enhancing the ERK pathway2023

    • Author(s)
      Asano Satoshi、Ono Ami、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Tanimoto Kotaro、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Peptides

      Volume: 161 Pages: 170940-170940

    • DOI

      10.1016/j.peptides.2023.170940

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overexpression of VIPR2 in mice results in microencephaly with paradoxical increased white matter volume2023

    • Author(s)
      Ago Y, Van C, Condro MC, Hrncir H, Diep AL, Rajbhandari AK, Fanselow MS, Hashimoto H, MacKenzie-Graham AJ, Waschek JA
    • Journal Title

      Experimental Neurology

      Volume: 362 Pages: 114339-114339

    • DOI

      10.1016/j.expneurol.2023.114339

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A new method for assessing depressive-like behaviors in female mice2023

    • Author(s)
      吾郷由希夫, 浅野智志
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 158 Issue: 1 Pages: 35-38

    • DOI

      10.1254/fpj.22101

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physicochemical and Biochemical Evaluation of Amorphous Solid Dispersion of Naringenin Prepared Using Hot-Melt Extrusion2022

    • Author(s)
      Ishimoto Kenji、Shimada Yukiko、Ohno Akane、Otani Shuichi、Ago Yukio、Maeda Soya、Lin Bangzhong、Nunomura Kazuto、Hino Nobumasa、Suzuki Masayuki、Nakagawa Shinsaku
    • Journal Title

      Frontiers in Nutrition

      Volume: 9 Pages: 850103-850103

    • DOI

      10.3389/fnut.2022.850103

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation2022

    • Author(s)
      Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y.
    • Journal Title

      Neurochemistry International

      Volume: 160 Pages: 105415-105415

    • DOI

      10.1016/j.neuint.2022.105415

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phospholipase C-related catalytically inactive protein enhances cisplatin-induced apoptotic cell death2022

    • Author(s)
      Asano Satoshi、Maetani Yuka、Ago Yukio、Kanematsu Takashi
    • Journal Title

      European Journal of Pharmacology

      Volume: 933 Pages: 175273-175273

    • DOI

      10.1016/j.ejphar.2022.175273

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vasoactive intestinal peptide?VIPR2 signaling regulates tumor cell migration2022

    • Author(s)
      Asano Satoshi、Yamasaka Misa、Ozasa Kairi、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Hashimoto Hitoshi、Waschek James A.、Ago Yukio
    • Journal Title

      Frontiers in Oncology

      Volume: 12 Pages: 852358-852358

    • DOI

      10.3389/fonc.2022.852358

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] AlphaFold version 2.0 elucidates the binding mechanism between VIPR2 and KS-133, and reveals an S-S bond (Cys25-Cys192) formation of functional significance for VIPR22022

    • Author(s)
      Sakamoto K, Asano S, Ago Y, Hirokawa T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 636 Pages: 10-16

    • DOI

      10.1016/j.bbrc.2022.10.071

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety and efficacy of an anti-claudin-5 monoclonal antibody to increase blood-brain barrier permeability for drug delivery to the brain in a non-human primate2021

    • Author(s)
      Tachibana K, Hashimoto Y, Shirakura K, Okada Y, Hirayama R, Iwashita Y, Nishino I, Ago Y, Takeda H, Kuniyasu H, Kondoh M
    • Journal Title

      Journal of Controlled Release

      Volume: 336 Pages: 105-111

    • DOI

      10.1016/j.jconrel.2021.06.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple alterations in glutamatergic transmission and dopamine D2 receptor splicing in induced pluripotent stem cell-derived neurons from patients with familial schizophrenia2021

    • Author(s)
      Yamamoto Kana、Kuriu Toshihiko、Takuma Kazuhiro、Ono Fumihito、Matsumoto Naomichi、Hashimoto Ryota、Hashimoto Hitoshi、Nakazawa Takanobu
    • Journal Title

      Translational Psychiatry

      Volume: 11 Issue: 1 Pages: 548-548

    • DOI

      10.1038/s41398-021-01676-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of KS-133 as a novel bicyclic peptide with a potent and selective VIPR2 antagonist activity that counteracts cognitive decline in a mouse model of psychiatric disorders2021

    • Author(s)
      Sakamoto K, Chen L, Miyaoka T, Yamada M, Masutani T, Ishimoto K, Hino N, Nakagawa S, Asano S, Ago Y
    • Journal Title

      Frontiers in Pharmacology

      Volume: 12 Pages: 751587-751587

    • DOI

      10.3389/fphar.2021.751587

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Probing the VIPR2 microduplication linkage to schizophrenia in animal and cellular models2021

    • Author(s)
      Ago Y, Asano S, Hashimoto H, Waschek JA
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 717490-717490

    • DOI

      10.3389/fnins.2021.717490

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PACAPシグナル系を介したストレスが誘発する精神疾患の発症機序の解明と治療薬の開発2021

    • Author(s)
      早田敦子, 吾郷由希夫, 橋本 均
    • Journal Title

      細胞

      Volume: 53 Pages: 60-63

    • NAID

      40022470686

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Activation of the VPAC2 Receptor Impairs Axon Outgrowth and Decreases Dendritic Arborization in Mouse Cortical Neurons by a PKA-Dependent Mechanism2020

    • Author(s)
      Takeuchi Shuto、Kawanai Takuya、Yamauchi Ryosuke、Chen Lu、Miyaoka Tatsunori、Yamada Mei、Asano Satoshi、Hayata-Takano Atsuko、Nakazawa Takanobu、Yano Koji、Horiguchi Naotaka、Nakagawa Shinsaku、Takuma Kazuhiro、Waschek James A.、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 521-532

    • DOI

      10.3389/fnins.2020.00521

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 精神神経機能障害における遺伝/環境因子の役割2020

    • Author(s)
      吾郷由希夫
    • Journal Title

      広島大学歯学雑誌

      Volume: 52 Pages: 55-61

    • NAID

      40022485269

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PACAPシグナル系を介したストレスが誘発する精神疾患の発症機序の解明と治療薬の開発2020

    • Author(s)
      早田敦子, 吾郷由希夫, 橋本 均
    • Journal Title

      Medical Science Digest

      Volume: 46 Pages: 54-57

    • NAID

      40022470686

    • Related Report
      2020 Annual Research Report
  • [Presentation] VIPR2特異的アンタゴニストとしての二環式中分子ペプチドKS-133の創製とマクロファージの極性変化による抗腫瘍効果2024

    • Author(s)
      坂元孝太郎, 都 英次郎, 中川晋作, 吾郷由希夫, 西山 成
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Role of the VPAC2 receptor overactivation implicated in schizophrenia susceptibility2023

    • Author(s)
      Ami Ono, Daichi Koan, Tatsunori Miyaoka, Satoshi Asano, Shinsaku Nakagawa, James A. Waschek, Kotaro Tanimoto, Yukio Ago
    • Organizer
      第56回広島大学歯学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 胎生期中枢神経系におけるVPAC2受容体の過剰発現は脳の萎縮と白質の増加、感覚情報処理機能の障害を引き起こす2023

    • Author(s)
      吾郷由希夫, Allan J. MacKenzie-Graham, 橋本 均, James A. Waschek
    • Organizer
      第143回日本薬理学会近畿部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 血管作動性腸管ペプチド受容体2シグナルはERK経路を介した乳癌細胞増殖に関与している2023

    • Author(s)
      浅野智志, 小野亜美, 坂元孝太郎, 早田敦子, 中澤敬信, 谷本幸太郎, 橋本 均, 吾郷由希夫
    • Organizer
      第143回日本薬理学会近畿部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] VPAC2受容体を標的とした新規の中分子による統合失調症治療薬の創出2023

    • Author(s)
      吾郷由希夫, 坂元孝太郎, 浅野智志
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 神経ペプチド受容体VIPR2の二量体化の機能的意義2023

    • Author(s)
      浅野智志, 小野亜美, 吾郷由希夫
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 統合失調症の発症脆弱性の解明を目指した神経細胞特異的VIPR2過剰発現マウスモデルの開発2023

    • Author(s)
      小野亜美, 浅野智志, 吾郷由希夫
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 統合失調症の新たな創薬標的分子:VPAC2受容体アンタゴニストペプチドの創製2023

    • Author(s)
      吾郷由希夫
    • Organizer
      第53回日本神経精神薬理学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Modeling VIPR2 linkage to schizophrenia and developing antipsychotic medication2023

    • Author(s)
      Yukio Ago
    • Organizer
      Taiwanase Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) 2023 Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Overexpression of VPAC2 receptors in the embryonic mouse central nervous system causes brain atrophy, increased white matter, and impaired sensorimotor gating2023

    • Author(s)
      Yukio Ago, Allan J. MacKenzie-Graham, Hitoshi Hashimoto, James A. Waschek
    • Organizer
      The 8th Congress of the Asian College of Neuropsychopharmacology (AsCNP)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 統合失調症の発症脆弱性因子としてのVPAC2受容体過活性化の役割―神経細胞特異的ヒトVPAC2受容体過剰発現マウスを用いた検討-2023

    • Author(s)
      小野亜美, 今戸瑛二, 吾郷由希夫
    • Organizer
      第40回日本障害者歯科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Oxytocin restores abnormal social behavior in a mouse model of 3q29 microdeletion2023

    • Author(s)
      Tomoya Takemoto, Kohei Kitagawa, Kazuki Nagayasu, Kaoru Seiriki, Atsuko Hayata-Takano, Atsushi Kasai, Yukio Ago, Kazuhiro Takuma, Daisuke Mori, Norio Ozaki, Ryota Hashimoto, Hitoshi Hashimoto, Takanobu Nakazawa
    • Organizer
      The 53rd Annual Meeting of the Society for Neuroscience (Neuroscience 2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] (R)-ketamine enhances anterior insular cortex activity associated with social cognition2023

    • Author(s)
      Rei Yokoyama, Yukio Ago, Masato Tanuma, Yuto Shimazaki, Kaoru Seiriki, Takanobu Nakazawa, Kenji Hashimoto, Atsushi Kasai, Hitoshi Hashimoto
    • Organizer
      The 53rd Annual Meeting of the Society for Neuroscience (Neuroscience 2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 二環式ペプチドKS-133とクラスB GPCR:VIPR2の結合メカニズム解明と機能的S-S結合の発見2023

    • Author(s)
      坂元孝太郎, 浅野智志, 吾郷由希夫, 広川貴次
    • Organizer
      第51回構造活性相関シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] 乳癌の増殖・転移における神経ペプチド受容体VIPR2 二量体化の機能的意義2023

    • Author(s)
      浅野智志, 小野亜美, 上原 輝, 谷本幸太郎, 柳本惣市, 吾郷由希夫
    • Organizer
      第40回創薬・薬理フォーラム岡山
    • Related Report
      2023 Annual Research Report
  • [Presentation] 神経ペプチド受容体VIPR2による乳癌細胞遊走・増殖の新たな制御機構2023

    • Author(s)
      浅野智志, 坂元孝太郎, 吾郷由希夫
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 治療抵抗性統合失調症の克服に向けた結合組織成長因子CTGFの役割と脳内デリバリー2023

    • Author(s)
      吾郷由希夫
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 非定型抗精神病薬クロザピンの認知機能障害改善作用における結合組織成長因子の関与2023

    • Author(s)
      金 子皓, 宮岡辰典, 山内良介, 竹内修斗, 河内琢也, 陳 露, 片平海雅, 石本憲司, 樋野展正, 早田敦子, 中澤敬信, 田熊一敞, 中川晋作, 橋本 均, 吾郷由希夫
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 神経ペプチド受容体VIPR2遺伝子のコピー数変異モデルマウスは超音波発声の変化と社会性行動の低下を示す2023

    • Author(s)
      片平海雅, 陳 露, 宮岡 辰典, 北川 航平, 竹内 修斗, 山田 めゐ, 金 子皓, 石本憲司, 塚本智仁, 樋野展正, 中澤敬信, 橋本 均, 中川晋作, 吾郷由希夫
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 精神疾患の治療を目指したVIPR2阻害剤の中分子創薬2023

    • Author(s)
      吾郷由希夫, 山田めゐ, 宮岡辰典, 陳 露, 石本憲司, 樋野展正, 中川晋作, 坂元孝太郎, 浅野智志
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒト染色体3q29領域欠失を導入した自閉スペクトラム症モデルマウスの社会性行動異常はオキシトシンの投与により回復する2023

    • Author(s)
      竹本智哉, 馬場優志, 北川航平, 永安一樹, 勢力 薫,早田敦子, 笠井淳司, 吾郷由希夫, 田熊一敞, 橋本亮太, 橋本 均, 中澤敬信
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Activation of the rostral agranular insular cortex is involved in the antidepressant actions of arketamine2022

    • Author(s)
      Yukio Ago, Rei Yokoyama, Atsushi Kasai, Masato Tanuma, Misuzu Hayashida, Yuto Shimazaki, Momoko Higuchi, Hisato Igarashi, Kaoru Seiriki, Shun Yamaguchi, Takanobu Nakazawa, Kenji Hashimoto, Hitoshi Hashimoto
    • Organizer
      The 61st Annual Meeting of the American College of Neuropsychopharmacology (ACNP)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Claustrum mediates stress-induced anxiety responses and stress resistance2022

    • Author(s)
      Hitoshi Hashimoto, Misaki Niu, Masato Tanuma, Kaoru Seiriki, Yukio Ago, Shun Yamaguchi, Atsushi Kasai
    • Organizer
      The 61st Annual Meeting of the American College of Neuropsychopharmacology (ACNP)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Agranular insular cortex mediates the antidepressant actions of arketamine2022

    • Author(s)
      Rei Yokoyama, Yukio Ago, Atsushi Kasai, Masato Tanuma, Misuzu Hayashida, Yuto Shimazaki, Momoko Higuchi, Hisato Igarashi, Kaoru Seiriki, Shun Yamaguchi, Takanobu Nakazawa, Kenji Hashimoto, Hitoshi Hashimoto
    • Organizer
      The 51st Annual Meeting of the Society for Neuroscience (Neuroscience 2022)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intranasal oxytocin administration suppresses social contact-induced neural activity in a POGZ-Q1038R mutant mouse model of autism spectrum disorder2022

    • Author(s)
      Kohei Kitagawa, Masayuki Baba, Tomoya Takemoto, Masato Tanuma, Misuzu Hayashida, Shun Yamaguchi, Yukio Ago, Kaoru Seiriki, Atsuko Hayata-Takano, Kazuhiro Takuma, Atsushi Kasai, Hitoshi Hashimoto, Takanobu Nakazawa
    • Organizer
      The 51st Annual Meeting of the Society for Neuroscience (Neuroscience 2022)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] KS-133, a novel peptide antagonist targeting VIPR2 for the treatment of schizophrenia2022

    • Author(s)
      Yukio Ago, Kotaro Sakamoto, Satoshi Asano
    • Organizer
      VPAC ISBAP 2022 (Joint symposium of the 1st Meeting of the International Society for Bioactive Peptides and the 15th International Symposium on VIP, PACAP and Related Peptides)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The VIP/VIPR2 pathway regulates breast cancer cell migration2022

    • Author(s)
      Satoshi Asano, Misa Yamasaka, Kairi Ozasa, Kotaro Sakamoto, Atsuko Hayata-Takano, Takanobu Nakazawa, Hitoshi Hashimoto, James A. Waschek, Yukio Ago
    • Organizer
      VPAC ISBAP 2022 (Joint symposium of the 1st Meeting of the International Society for Bioactive Peptides and the 15th International Symposium on VIP, PACAP and Related Peptides)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neuron-specific overexpression of human VPAC2 receptors in mice causes cognitive dysfunction2022

    • Author(s)
      Ami Ono, Daichi Koan, Satoshi Asano, Tatsunori Miyaoka, Lu Chen, Mei Yamada, Shinsaku Nakagawa, Atsuko Hayata-Takano, Takanobu Nakazawa, Akihiro Harada, Hitoshi Hashimoto, James A. Waschek, Yukio Ago
    • Organizer
      VPAC ISBAP 2022 (Joint symposium of the 1st Meeting of the International Society for Bioactive Peptides and the 15th International Symposium on VIP, PACAP and Related Peptides)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impaired neurodevelopment in iPS cell-derived neural stem cells from psychiatric patients with 7q36.3 microduplication2022

    • Author(s)
      Kohei Kitagawa, Masayuki Baba, Tomoya Takemoto, Kazuki Nagayasu, Atsushi Kasai, Kazuhiro Takuma, Ryota Hashimoto, Hitoshi Hashimoto, Yukio Ago, Takanobu Nakazawa
    • Organizer
      VPAC ISBAP 2022 (Joint symposium of the 1st Meeting of the International Society for Bioactive Peptides and the 15th International Symposium on VIP, PACAP and Related Peptides)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自閉スペクトラム症の新しい治療戦略:社会性障害の回復機構における脳部位特異的オピオイドシステムバランスの役割2022

    • Author(s)
      吾郷由希夫
    • Organizer
      第96回日本薬理学会年会・第43回日本臨床薬理学会学術総会 合同大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 自閉スペクトラム症の病態基盤解明と創薬を目指して2022

    • Author(s)
      吾郷由希夫
    • Organizer
      第39回日本障害者歯科学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] A potential role of neuropeptide receptor VIPR2 signaling in tumor cell migration2022

    • Author(s)
      Satoshi Asano, Misa Yamasaka, Kairi Ozasa, James Waschek, Yukio Ago
    • Organizer
      第55回広島大学歯学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Abnormal pain sensitivity associated with spinal microglial activation in a prenatal valproic acid-induced mouse model of autism2022

    • Author(s)
      Eiji Imado, Sun Samnang, Abrar Rizal Abawa, Satoshi Asano, Kazuhiro Tsuga, Masahiro Irifune, Yukio Ago
    • Organizer
      第55回広島大学歯学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] マウス胎生期のバルプロ酸曝露は脊髄でのミクログリアの増殖とアロディニアを引き起こす2022

    • Author(s)
      吾郷由希夫, 今戸瑛二, Samnang Sun, 中村庸輝, 中島一恵, 森岡徳光, 田熊一敞, 木口倫一, 浅野智志
    • Organizer
      Neuro2022 (第45回日本神経科学大会・第65回日本神経化学会大会・第32回日本神経回路学会大会 合同大会)
    • Related Report
      2022 Annual Research Report
  • [Presentation] Possible role of histone deacetylase inhibition in tactile hypersensitivity in a mouse model of autism spectrum disorder2022

    • Author(s)
      Samnang Sun, Eiji Imado, Tran Ngoc Bao Huynh, Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka, Norikazu Kiguchi, Satoshi Asano, Yukio Ago
    • Organizer
      第37回創薬・薬理フォーラム岡山
    • Related Report
      2022 Annual Research Report
  • [Presentation] 神経ペプチド受容体VIPR2はPI3K経路を介してがん細胞遊走を制御する2022

    • Author(s)
      浅野智志, 吾郷由希夫
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 自閉スペクトラム症モデルマウスにおける持続的なアロディニアの発現と脊髄内ミクログリア活性化の関与2022

    • Author(s)
      今戸瑛二, 入舩正浩, 吾郷由希夫
    • Organizer
      第50回日本歯科麻酔学会総会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 鎮痛作用を示さない低用量μオピオイド受容体アゴニストは自閉スペクトラム症モデルマウスの社会性行動障害を改善する2022

    • Author(s)
      吾郷由希夫, 内藤 恵, 川瀬啓生, 樋口桃子, 山川英訓, 大波壮一郎, 小川公一, 中邨篤史, 河内貴弘, 今戸瑛二, 田原 孟, 浅野智志, 古武弥一郎, 田熊一敞, 橋本 均
    • Organizer
      第44回日本生物学的精神医学会年会、第32回日本臨床精神神経薬理学会年会、第52回日本神経精神薬理学会年会、第6回日本精神薬学会総会・学術集会 4学会合同年会(BPCNPNPPP4学会合同年会)
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎生期のヒストン脱アセチル化酵素阻害は脊髄ミクログリアの活性化と機械的アロディニアを引き起こす2022

    • Author(s)
      今戸瑛二, Sun Samnang, Huynh Ngoc Bao Tran, 中村庸輝, 中島一恵, 森岡徳光, 木口倫一, 浅野智志, 吾郷由希夫
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] TRPV1アンタゴニストAMG517は胎生期バルプロ酸投与誘発の自閉症モデルマウスにおいて痛覚感受性の異常と社会性行動障害を改善する2022

    • Author(s)
      田原 孟, 今戸瑛二, 川瀬啓生, 樋口桃子, 山川英訓, 小川公一, 古武弥一郎, 田熊一敞, 橋本 均, 浅野智志, 吾郷 由希夫
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] PLC様タンパク質PRIP1のPH domain内包リポソームはシスプラチン耐性乳ガン細胞のアポトーシス細胞死を促進する2022

    • Author(s)
      浅野智志, 吾郷由希夫, 兼松 隆
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] アールケタミンの抗うつ作用発現には島皮質が関与する2022

    • Author(s)
      横山 玲, 吾郷由希夫, 笠井淳司, 田沼将人, 林田美鈴, 島﨑雄人, 樋口桃子, 五十嵐久人, 勢力 薫, 山口 瞬, 中澤敬信, 橋本謙二, 橋本 均
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 統合失調症治療を目指したクラスB GPCR VIPR2アンタゴニストペプチドの薬理学的研究2022

    • Author(s)
      吾郷由希夫, 坂元孝太郎
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 抗うつ薬・抗うつ薬候補の反応性からみるモデル動物の役割2022

    • Author(s)
      吾郷由希夫
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 神経ペプチド受容体VIPR2のオリゴマー化とその機能的意義2022

    • Author(s)
      浅野智志, 小笹かいり, 中澤敬信, Waschek James, 吾郷由希夫
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 神経ペプチドVIPはVPAC2受容体を介するPI3K経路の活性化により細胞遊走を引き起こす2022

    • Author(s)
      小笹かいり, 浅野智志, 山坂美紗, 早田敦子, 中澤敬信, 橋本 均, Waschek James, 吾郷由希夫
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 神経発達障害モデルマウスにおける機械的アロディニアの発症とミクログリアの関与2022

    • Author(s)
      今戸瑛二, Samnang Sun, Abawa Abrar, 浅野智志, 中村庸輝, 中島一恵, 森岡徳光, 津賀一弘, 入舩正浩, 田熊一敞, 木口倫一, 吾郷由希夫
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ASDモデルマウスの社会性行動と前頭前皮質の機能異常2022

    • Author(s)
      笠井淳司, 彌永祐輔, 植野寛貴, 中井悠花, 原 雄大, 三浦大樹, 田沼将人, 林田美鈴, 横山 玲, 大久保 仁, 勢力 薫, 早田-高野敦子, 山口 瞬, 北岡志保, 古屋敷智之, 吾郷由希夫, 中澤敬信, 田熊一敞, 橋本 均
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 精神疾患の創薬を目指した脳研究~マウスでみてきたこと~2021

    • Author(s)
      吾郷由希夫
    • Organizer
      第40回躁うつ病の薬理・生化学的研究懇話会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] レアバリアントから迫る精神疾患の病態解明と創薬研究2021

    • Author(s)
      吾郷由希夫
    • Organizer
      第36回創薬・薬理フォーラム岡山
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] A potent and highly selective VPAC2 receptor antagonist peptide KS-133 counteracts cognitive impairment in a mouse model relevant to schizophrenia2021

    • Author(s)
      Yukio Ago, Lu Chen, Tatsunori Miyaoka, Mei Yamada, Teruaki Masutani, Kenji Ishimoto, Shinsaku Nakagawa, Satoshi Asano, Kotaro Sakamoto
    • Organizer
      The 60th Annual Meeting of the American College of Neuropsychopharmacology (ACNP)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Overexpression of VIPR2 in neurons causes defects in dendritic growth and cognitive impairment2021

    • Author(s)
      Tatsunori Miyaoka, Lu Chen, Mei Yamada, Daichi Koan, Satoshi Asano, Kenji Ishimoto, Shinsaku Nakagawa, Atsuko Hayata, Takanobu Nakazawa, Akihiro Harada, Hitoshi Hashimoto, James A. Waschek, Yukio Ago
    • Organizer
      The 7th Congress of the Asian College of Neuropsychopharmacology (AsCNP)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Abnormal pain sensitivity in a prenatal valproic acid-induced mouse model of autism spectrum disorder2021

    • Author(s)
      Eiji Imado, Sun Samnang, Abrar Rizal Abawa, Satoshi Asano, Kazuhiro Tsuga, Masahiro Irifune, Yukio Ago
    • Organizer
      The 6th Joint Scientific Meeting in Dentistry
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胎生期バルプロ酸投与マウスは熱刺激およびカプサイシン誘発痛の増大と機械的アロディニアを示す2021

    • Author(s)
      今戸瑛二, 浅野智志, 中村庸輝, 中島一恵, 森岡徳光, 津賀一弘, 入舩正浩, 田熊一敞, 吾郷由希夫
    • Organizer
      第139回日本薬理学会近畿部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトVPAC2受容体の過剰発現を細胞種特異的かつ時空間的に制御可能な新しいトランスジェニックマウスモデルの開発2021

    • Author(s)
      宮岡辰典, 陳 露, 山田めゐ, 古庵大地, 浅野智志, 石本憲司, 中川晋作, 早田敦子, 中澤敬信, 原田彰宏, 橋本 均, Waschek James, 吾郷由希夫
    • Organizer
      第43回日本生物学的精神医学会・第51回日本神経精神薬理学会 合同年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 7q36.3領域微小重複を有する精神疾患患者のiPS細胞由来分化神経幹細胞を用いた分子病態解析2021

    • Author(s)
      北川航平, 馬場優志, 竹本智哉, 永安一樹, 笠井淳司, 橋本亮太, 橋本 均, 吾郷由希夫, 中澤敬信
    • Organizer
      生体機能と創薬シンポジウム2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 7q36.3領域微小重複を有する精神疾患患者のiPS細胞由来分化神経幹細胞を用いた分子病態解析2021

    • Author(s)
      北川航平, 馬場優志, 竹本智哉, 永安一樹, 笠井淳司, 橋本亮太, 橋本 均, 吾郷由希夫, 中澤敬信
    • Organizer
      次世代を担う若手のための創薬・医療薬理シンポジウム2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規選択的VPAC2受容体アンタゴニストペプチドの創製とその中枢薬理作用2021

    • Author(s)
      山田めゐ, 陳 露, 宮岡辰典, 桝谷晃明, 石本憲司, 樋野展正, 中川晋作, 浅野智志, 坂元孝太郎, 吾郷由希夫
    • Organizer
      第140回日本薬理学会近畿部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒト染色体3q29領域欠失を導入した自閉スペクトラム症モデルマウスの社会性行動異常はオキシトシンの投与により回復する2021

    • Author(s)
      竹本智哉, 馬場優志, 北川航平, 永安一樹, 勢力 薫, 早田敦子, 笠井淳司, 吾郷由希夫, 田熊一敞, 橋本 均, 中澤敬信
    • Organizer
      第140回日本薬理学会近畿部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 生体内で薬効を示す VIPR2 選択的アンタゴニストペプチドの創製2021

    • Author(s)
      坂元孝太郎, 吾郷由希夫
    • Organizer
      第16回GPCR研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] オキシトシンの鼻腔内投与はPOGZ-Q1038R点変異マウスの社会性行動異常を改善する2021

    • Author(s)
      北川航平, 松村憲佑, 馬場優志, 近藤百香, 竹本智哉, 永安一樹, 吾郷由希夫, 笠井淳司, 田熊一敞, 橋本 均, 中澤敬信
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脳神経細胞でのVPAC2受容体の過剰発現は認知機能障害を引き起こす2021

    • Author(s)
      古庵大地, 今戸瑛二, 浅野智志, Chen Lu, 宮岡辰典, 山田めゐ, 石本憲司, 中川晋作, 早田敦子, 中澤敬信, 原田彰宏, 橋本 均, Waschek James, 吾郷由希夫
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Behavioral and morphological abnormalities in a mouse model with copy number variation of the vasoactive intestinal peptide receptor VIPR2 gene2020

    • Author(s)
      陳 露, 竹内修斗, 山田めゐ, 宮岡辰典, 山口拓海, 中澤敬信, 中川晋作, 橋本 均, 吾郷由希夫
    • Organizer
      第137回日本薬理学会近畿部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト染色体3q29欠失モデルマウスを用いた精神疾患の分子病態研究2020

    • Author(s)
      馬場優志, 勢力 薫, 近藤百香, 北川航平, 竹本智哉, 笠井淳司, 吾郷由希夫, 永安一樹, 森 大輔, 尾崎紀夫, 山本 雅, 田熊一敞, 橋本亮太, 橋本 均, 中澤敬信
    • Organizer
      第138回日本薬理学会近畿部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 妊娠期の薬物服用に起因する自閉スペクトラム症の病態解明2020

    • Author(s)
      田熊一敞, 原 雄大, 吾郷由希夫, 橋本 均, 中澤敬信, 松田敏夫
    • Organizer
      第50回日本神経精神薬理学会年会, 第42回日本生物学的精神医学会年会, 第4回日本精神薬学会総会・学術集会 合同年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] レアバリアントから迫る統合失調症の病態分子基盤と創薬戦略2020

    • Author(s)
      吾郷由希夫
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Remarks] 広島大学歯学部細胞分子薬理学

    • URL

      https://www.hiroshima-u.ac.jp/dent/research/lab/dentistry/Cellular_and_Molecular_Pharmacology

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] 広島大学研究者総覧

    • URL

      https://seeds.office.hiroshima-u.ac.jp/profile/ja.a6cd938e58eb0f72520e17560c007669.html

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 組成物2023

    • Inventor(s)
      坂元孝太郎, 都英次郎, 吾郷由希夫, 中川晋作
    • Industrial Property Rights Holder
      坂元孝太郎, 都英次郎, 吾郷由希夫, 中川晋作
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-223187
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] 癌転移抑制用のVIPR2アンタゴニストペプチド2022

    • Inventor(s)
      吾郷由希夫, 浅野智志, 坂元孝太郎
    • Industrial Property Rights Holder
      吾郷由希夫, 浅野智志, 坂元孝太郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-027791
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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