GABAergic inhibitory control of synaptic plasticity and anesthetic actions in the brain: molecular basis of hypnotic action and neurotoxicity of general anesthetics

• Project/Area Number: 26462341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Fukushima Medical University
• Principal Investigator: Nishikawa Koichi 福島県立医科大学, 公私立大学の部局等, 研究員 (00334110)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 麻酔 / GABA受容体 / 可塑性 / 鎮静 / 神経毒性 / 麻酔薬 / GABA 受容体 / シナプス / GABA / 鎮痛 / セボフルラン / トランスポーター / Glycine / 神経伝達物質 / 中枢抑制

Outline of Final Research Achievements

Aim of Investigation: GABA and glycine are principal inhibitory neurotransmitters in the central nervous system and are laded into synaptic visicles via the vesicular GABA transporter (VGAT). We have found that VGAT+/- mice showed enhanced sensitivity to thermal stimulation and chemical inflammation. We investigated the possible influence of down-regulation of VGAT on hypnotic and analgesic actions of sevoflurane and propofol in mice. Results and Discussion: Reduction of VGAT protein (about half of the normal) doesn't affect hypnotic/analgesic effect of sevoflurane on mice behavior. This result shows Sevoflurane can enhance the inhibitory system (sedation/analgesia) by the effect on postsynaptic receptors despite of the decreased loading inhibitory neurotransmitters into synaptic vesicles.Although this study demonstrated that growth/development and ansthetic sensitivity are the same between VGAT(+/-) and WT, VGAT protein has been the important potential target of anesthetic drugs.

Research Products

• [Journal Article] In-hospital mortality does not increase in patients aged over 85 years after hip fracture surgery. A retrospective observational study in a Japanese tertiary hospital. (2018)
  • Author(s): Fujita Y, Shimada K, Sato T, Akatsu M, Nishikawa K, Kanno A, Aizawa T
  • Journal Title: JA Clinical Reports Volume: 4 Pages: 36-39
  • Peer Reviewed
• [Journal Article] Anesthetic Management of a Patient With Antimuscle-Specific Kinase Antibody-Positive Myasthenia Gravis Undergoing an Open Cholecystectomy: A Case Report. (2017)
  • Author(s): Akatsu M, Ikegami Y, Tase C, Nishikawa K
  • Journal Title: A A Case Rep. Volume: 8 Issue: 6 Pages: 150-153
  • DOI: 10.1213/xaa.0000000000000453
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] In-hospital mortality does not increase in patients aged over 85 years after hip fracture surgery. A retrospective observational study in a Japanese tertiary hospital. (2017)
  • Author(s): Fujita Y, Shimada K, Sato T, Akatsu M, Nishikawa K, Kanno A, Aizawa T
  • Organizer: American Society of Anesthesiologists (ASA) meeting
  • Int'l Joint Research
• [Presentation] The role of vesicular GABA transporter (VGAT) in hypnotic and analgesic actions of general anesthetics (2016)
  • Author(s): Komatsu S, Nishikawa K
  • Organizer: 16th World Congress on Pain
  • Place of Presentation: Yokohama
  • Int'l Joint Research
• [Presentation] デスフルランのTc-MEP, SSEPにおける有用性： 10症例の脊椎手術からの検討 (2015)
  • Author(s): 赤津 賢彦、根本 千秋、池上 之浩、西川 光一、栗原 正人、田勢 長一郎
  • Organizer: 日本麻酔科学会第62回学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2015-05-29
• [Presentation] 東日本大震災により変化した麻酔科医の環境―当院の麻酔科管理症例数の推移と状況－ (2015)
  • Author(s): 赤津 賢彦、根本 千秋、池上 之浩、西川 光一、栗原 正人、田勢 長一郎
  • Organizer: 日本麻酔科学会第62回学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2015-05-29
• [Presentation] 抗筋特異的チロシンキナーゼ(MuSK) 抗体陽性重症筋無力症(MG) を合併する開腹胆嚢摘出術の麻酔経験 (2014)
  • Author(s): 赤津賢彦、根本千秋、池上之浩、西川光一、田勢長一郎
  • Organizer: 日本臨床麻酔学会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-01 – 2014-11-03
• [Presentation] セボフルランの鎮痛・鎮静作用における小胞型GABA/Glycineトランスポーター (VGAT)の役割 (2014)
  • Author(s): 小松秀一郎、西川光一
  • Organizer: 日本麻酔科学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-05-15 – 2014-05-17