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
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Anesthesiology
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| Research Institution | Fukushima Medical University |
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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)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥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)
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| 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 |
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| 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.
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Report
(5 results)
Research Products
(8 results)
