Study on the function of D-serine of synaptic transmission in the spinal dorsal horn.

• Project/Area Number: 18K16462
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: KATO EIKO 獨協医科大学, 医学部, 助教 (10721897)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 神経障害性痛 / D-セリン / 脊髄後角シナプス / NMDA受容体 / Serine racemase / Spinal dorsal horn / Spinal nerve ligation / Whole-cell recording / NMDA receptor / Chung method / Nociceptive behavior / Mechanical allodynia / Neuropathic pain / セリンラセマーゼ / パッチクランプ記録法 / 神経障害性疼痛 / 機械的侵害受容刺激

Outline of Final Research Achievements

The present analysis showed the following:
1) The NMDA receptor-mediated neurotransmission was altered in the SDH of the intact SR-KO mice. The synaptic charge transferred during NMDA-EPSC was significantly larger in SR-KO mice than WT mice. 2) Behavioral observations showed the mechanical allodynia in the Chung model was significantly augmented in SR-KO mice compared with WT mice. 3)The synaptic charge transferred during NMDA-EPSC was increased in the nerve-ligated SR-KO mice compared to the intact SR-KO mice.

Academic Significance and Societal Importance of the Research Achievements

神経障害性痛は多様な症状を引き起こす難治性の慢性疼痛であり、神経障害性痛の発症メカニズムの解明とその鎮痛法の開発は世界的に重要な課題である。本研究では、SR-KOマウスを用い、内因性D-セリンが神経障害性痛の発症にどのように機能しているか、脊髄における機能をシナプス伝達レベルで電気生理学的に明らかにした。この研究成果は神経障害性痛の発症機序解明に有用な結果をもたらし、既存の鎮痛法に抵抗性である難治性疼痛の新たな治療法の開発に貢献すると考えられる。

Research Products

• [Journal Article] Effects of peripheral nerve injury on the kinetics of electrically evoked GABA receptor-mediated currents in GABAergic and non-GABAergic neurons of the spinal dorsal horn (2022)
  • Author(s): Takaaki Ajima, Shigeki Yamaguchi, Toshifumi Takasusuki, Eiko Kato, Yuuichi Hori
  • Journal Title: Dokkyo Medical Journal Volume: -
  • Peer Reviewed
• [Journal Article] Pre and post synaptic mechanisms about the peripheral nerve-injured plasticity of nociceptive transmission in the superficial dorsal horn of mouse spinal cord (2021)
  • Author(s): Yuya Sato, Takaaki Ajima, Toshifumi Takasusuki, Eiko Kato, Yuuichi Hori, Shigeki Yamaguchi
  • Journal Title: Dokkyo Journal of Medical Sciences Volume: 48 Pages: 23-31
  • Peer Reviewed
• [Presentation] Comparisons of Nociceptive Behavior and NMDA receptor-Mediated Synaptic Transmission between Mice Lacking D-Serine Production and Degradation Enzymes (2020)
  • Author(s): Eiko Kato, Toshiya Saotome, Shigeki Yamaguchi, Kenji Kansaku, Yuuichi Hori
  • Organizer: Experimental Biology meeting 2020
  • Int'l Joint Research
• [Presentation] Comparison of effects of serine racemase knockout on nociceptive behavior among different models of neuropathic and inflammatory pain (2018)
  • Author(s): Eiko Kato, Toshiya Saotome, Teruyuki Fukushima, Toshifumi Takasusuki, Shigeki Yamaguchi, Yuuichi Hori
  • Organizer: Experimental Biology meeting 2018
  • Int'l Joint Research
• [Presentation] Different effects of deletion of the serine racemase gene on nociceptive behavior among different models of neuropathic and inflammatory pain (2018)
  • Author(s): Eiko Kato, Teruyuki Fukushima, Masao Maekawa, Yuuichi Hori
  • Organizer: The 48th Annual Meeting of the Society for Neuroscience
  • Int'l Joint Research