Search for rapid-acting antidepressant using MEA-based co-culture systems

• Project/Area Number: 16H03162
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: The University of Tokyo
• Principal Investigator: Jimbo Yasuhiko 東京大学, 大学院工学系研究科(工学部), 教授 (20372401)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 脳神経疾患 / 細胞・組織 / シグナル伝達 / ナノバイオ

Outline of Final Research Achievements

Rapid-acting antidepressant was searched using MicroElectrode-Array (MEA) -based neuronal ensemble recording system. In addition to ketamine, which has clear antidepressant effect but with limited use due to its side effects, memantine (no antidepressant effect, no side effect), lanicemine (weak antidepressant effect) were applied. The bursting neurons in cortical cells showed a specific pharmacological response, which might underlie rapid antidepressant mechanisms. The next step will be to identify the subunit composition of the NMDA receptors on these neurons.

Academic Significance and Societal Importance of the Research Achievements

現在一般に用いられている抗うつ薬は効果が現われるまでに数週間を要するという課題があり，即効性抗うつ効果を有するが副作用ゆえに使用が制限されているケタミンに代わる薬理活性物質が求められている．本研究では培養系に維持した神経細胞群を利用して，ケタミンを含む3種類の薬物の作用を調べた．大脳皮質に含まれる多様な細胞の中で特定のグループが特殊な薬理応答を示すという結果が得られた．この細胞群を特定し，関与する受容体のサブユニット構成などを調べることにより，抗うつ効果を発揮するメカニズムの理解が進み，新たな薬理活性物質の探索が期待できる．

Research Products

• [Journal Article] A co-culture microtunnel technique demonstrating a significant contribution of unmyelinated Schwann cells to the acceleration of axonal conduction in Schwann cell-regulated peripheral nerve development (2017)
  • Author(s): Sakai K. Shimba K., Kotani K., Jimbo Y.
  • Journal Title: Integr. Biol. Volume: 9 Issue: 8 Pages: 678-686
  • DOI: 10.1039/c7ib00051k
  • Peer Reviewed
• [Journal Article] Neurogenesis enhances response specificity to spatial pattern stimulation in hippocampal cultures (2017)
  • Author(s): Tanaka Y, Isomura T, Shimba K, Kotani K, Jimbo Y.
  • Journal Title: IEEE Trans Biomed Eng. Volume: 印刷中 Issue: 11 Pages: 2555-2561
  • DOI: 10.1109/tbme.2016.2639468
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ケタミンの神経回路網における薬理効果と神経細胞の活動パターンの関係 (2019)
  • Author(s): 加藤，榛葉，朝比奈，張，小谷，神保
  • Organizer: 電気学会医用・生体工学研究会
• [Presentation] 培養神経細胞の成熟度評価に向けた軸索薬理刺激デバイスの開発 (2019)
  • Author(s): 榛葉，酒井，小谷，神保
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] Microtunnel-based recording for evaluating axon conduction change after chemical treatment (2018)
  • Author(s): Shimba K., Sakai K., Kotani K., Jimbo Y.
  • Organizer: BMEiCON2018
  • Int'l Joint Research
• [Presentation] Microelectrode array with microtunnel structures for recording axon conduction from neuronal networks (2018)
  • Author(s): Shimba K., Sakai K., Kotani K., Jimbo Y.
  • Organizer: Volga Neuroscience Meeting
  • Int'l Joint Research
• [Presentation] Axon conduction changes by partial blockade of Na+ channels revealed with microtunnel-coupled MEA (2018)
  • Author(s): Shimba K., Sakai K., Kotani K., Yagi T., Jimbo Y.
  • Organizer: 11th Int. Meet. Substrate-Integrated Microelectrode Arrays
  • Int'l Joint Research
• [Presentation] アルツハイマー病進行機序理解に向けたアミロイドβによるiPSC神経ネットワークへの影響評価 (2018)
  • Author(s): 浦田,榛葉,飯田,酒井,小谷,神保
  • Organizer: 電気学会医用・生体工学研究会
• [Presentation] Microdevice for recording and pharmacological treatment to neural axons elongating into microtunnels (2017)
  • Author(s): Shimba K., Sakai K., Kotani K., Yagi T., Jimbo Y.
  • Organizer: Int. Conf. BioSensors, BioElectronics, BioMedical Devices
  • Int'l Joint Research
• [Presentation] Microtunnel-electrode device for elucidating axon features: toward pharmacological manipulation of individual axons (2017)
  • Author(s): Shimba K., Sakai K., Kotani K., Yagi T., Jimbo Y.
  • Organizer: 8th Int. IEEE EMBS Conf. Neural Engineering, Shanghai
  • Int'l Joint Research
• [Presentation] ケタミンの抗うつ作用の解明に向けた微小電極アレイ上への海馬-大脳皮質共培養系の構築 (2017)
  • Author(s): 味岡,酒井,小谷,神保
  • Organizer: 電気学会医用・生体工学研究会
  • Place of Presentation: 東京大学（東京都目黒区）