A novel mechanism for the development of stress-related psychiatric disorders

• Project/Area Number: 17H05054
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pharmacology in pharmacy
• Research Institution: Osaka University
• Principal Investigator: Kasai Atsushi 大阪大学, 薬学研究科, 准教授 (40454649)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000); Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2017: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
• Keywords: ストレス / 全脳 / 不安 / うつ / 精神疾患 / G-CaMP / 前障 / 情動 / 神経薬理 / 全脳イメージング / 情動障害 / 神経薬理学

Outline of Final Research Achievements

Although mental stress can cause the onset of psychiatric disorders such as depression, the pathogenesis of these disorders remains unclear. Here, we combined whole-brain activation mapping and data-driven analysis by support vector machine to identify a new population of neurons involved in the stress response and subsequent development of depression-like behavior. We have clarified the neuronal connectivity of the cell population to stress circuits at the whole brain level, and showed that specific neural manipulation of the cell population can mediate bidirectional and reversible control of stress-induced anxiety-related behavior and the onset of depressive-like behaviors. These results suggest that the cell population can be a therapeutic target for stress-related psychiatric disorders.

Academic Significance and Societal Importance of the Research Achievements

不安症やうつ病の新規治療薬の第一選択薬は、選択的セロトニン再取り込み阻害薬であり、過去数十年間新薬は出ていない。しかし、うつ病患者の約3割は、既存の抗うつ薬では治療効果が得られない難治性であるとされている。そのため、新たな機序の抗うつ薬・不安症等の治療薬開発が求められている。本研究によって同定されたストレス応答性の細胞集団は、これらストレス性精神疾患の新たな標的になることが期待される。

Research Products

• [Journal Article] Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain (2020)
  • Author(s): Masato Tanuma, Atsushi Kasai, Kazuki Bando, Naoyuki Kotoku, Kazuo Harada, Masafumi Minoshima, Kosuke Higashino, Atsushi Kimishima, Masayoshi Arai, Yukio Ago, Kaoru Seiriki, Kazuya Kikuchi, Satoshi Kawata, Katsumasa Fujita, Hitoshi Hashimoto
  • Journal Title: JCI Insight Volume: 5 Issue: 6
  • DOI: 10.1172/jci.insight.133348
  • Peer Reviewed / Open Access
• [Journal Article] Whole-brain block-face serial microscopy tomography at subcellular resolution using FAST. (2019)
  • Author(s): Seiriki K, Kasai A, Nakazawa T, Niu M, Naka Y, Tanuma M, Igarashi H, Yamaura K, Hayata-Takano A, Ago Y, Hashimoto H.
  • Journal Title: Nat Protoc. Volume: 印刷中 Issue: 5 Pages: 1509-1529
  • DOI: 10.1038/s41596-019-0148-4
  • Peer Reviewed / Open Access
• [Journal Article] High-speed and scalable whole-brain imaging in rodents and primates (2017)
  • Author(s): Seiriki K, Kasai A, Hashimoto T, Schulze W, Niu M, Yamaguchi S, Nakazawa T, Inoue K, Uezono S, Takada M, Naka Y, Igarashi H, Tanuma M, Waschek JA, Ago Y, Tanaka KF, Hayata-Takano A, Nagayasu K, Shintani N, Hashimoto R, Kunii Y, Hino M, Matsumoto J, Yabe H, Nagai T, Fujita K, Matsuda T, Takuma K, Baba A, Hashimoto H
  • Journal Title: Neuron Volume: 94 Issue: 6 Pages: 1085-1100
  • DOI: 10.1016/j.neuron.2017.05.017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Activation of claustral glutamatergic neurons induces anxiety-like behaviors through catecholamine release (2019)
  • Author(s): Atsushi Kasai et al
  • Organizer: 第92回 日本薬理学会年会
• [Presentation] Claustrum is involved in stress-induced anxiety-like behaviors (2018)
  • Author(s): Atsushi Kasai et al
  • Organizer: Cold Spring Harbor meeting: Molecular Mechanisms of neuronal connectivity
  • Int'l Joint Research
• [Presentation] FAST, High-speed serial-sectioning imaging for whole brain analysis with high scalability (2017)
  • Author(s): Kasai A et al,
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Presentation] FAST, high-speed serial-sectioning imaging for whole-brain analysis with high-scalability (2017)
  • Author(s): Atsushi Kasai
  • Organizer: 次世代薬理学セミナー
  • Invited
• [Presentation] 脳研究を加速する全脳イメージングシステムFAST (2017)
  • Author(s): 笠井淳司
  • Organizer: 日本薬学会東海支部特別講演
  • Invited
• [Presentation] 高速・高精細全脳イメージング法FASTの開発―新たな中間表現型の探索へ― (2017)
  • Author(s): 笠井淳司
  • Organizer: 第49回藤田学園医学会 研究最前線セミナー
  • Invited
• [Remarks] 大阪大学大学院薬学研究科 神経薬理学分野ホームページ
  • URL: http://molpharm.umin.jp/
• [Remarks] 大阪大学大学院薬学研究科神経薬理学分野
  • URL: http://molpharm.umin.jp/