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2017 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number 26462341
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionFukushima 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

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Published: 2019-03-29  

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