Extracellular signal regulated kinase has important roles in the regulating GABA A receptor activity

• Project/Area Number: 18K16503
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: National Defense Medical College
• Principal Investigator: ARAKI YOSHIYUKI 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 防衛医学, 助教 (30757894)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 麻酔 / ERK / GABA / ERK2 / 全身麻酔薬 / erk / gaba / GABA受容体 / 麻酔薬

Outline of Final Research Achievements

Intravenous anesthetics are widely used for surgery, but molecular mechanisms of anesthesia remain unidentified. Extracellular signal regulated kinases (ERKs) has important roles for cell signaling. In neurons, ERKs regulate several neuronal activities and here we investigated the roles of ERKs in the molecular mechanisms of action of intravenous anesthetics. We generated mice with Cre-loxP-mediated deletion of Erk2 in the central nervous systems and found that GABA (A) receptor activity is impaired in these mice. Accumulated evidence has indicated that the molecular target of intravenous anesthetics in the central nervous system is the GABA (A) receptor, the major mediator of inhibitory synaptic transmission. This result indicated that extracellular signal regulated kinase has important roles in the regulating GABA (A) receptor activity.

Academic Significance and Societal Importance of the Research Achievements

静脈麻酔薬プロポフォールはγアミノ酪酸（γaminobutyric acid：GABA）A受容体サブユニットに結合すると考えられているが、GABA（A）受容体の発現がどのような分子メカニズムで調節され、さらにどのようにしてプロポフォールによる麻酔作用とどのように関わっているかについては未だに不明な点が多かった。本研究の結果はERKが全身麻酔の作用機序において重要な役割を果たしていることを示唆しており、今後の全身麻酔薬開発などに資する可能性がある。

Research Products

• [Journal Article] Molecular hydrogen prevents social deficits and depression-like behaviours induced by low-intensity blast in mice. (2018)
  • Author(s): Satoh Y, Araki Y, Kashitani M, Nishii K, Kobayashi Y, Fujita M, Suzuki S, Morimoto Y, Tokuno S, Tsumatori G, Yamamoto T, Saitoh D, Ishizuka T.
  • Journal Title: J Neuropathol Exp Neurol Volume: 77 Issue: 9 Pages: 827-836
  • DOI: 10.1093/jnen/nly060
  • Peer Reviewed