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

2017 Fiscal Year Final Research Report

• 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
• Keywords: 麻酔 / GABA受容体 / 可塑性 / 鎮静 / 神経毒性

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.

Free Research Field

麻酔科学・神経科学・神経薬理学