General anesthesia impairs learning via the saturation of synaptic plasticity.
Project/Area Number |
24592308
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Anesthesiology/Resuscitation studies
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Research Institution | Yokohama City University |
Principal Investigator |
INAGAWA GAKU 横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (60336584)
|
Co-Investigator(Kenkyū-buntansha) |
GOTO Takahisa 横浜市立大学, 医学(系)研究科(研究院), 教授 (00256075)
UCHIMOTO Kazuhiro 横浜市立大学, 医学(系)研究科(研究院), 共同研究員 (50710951)
TAKAHASI Takuya 横浜市立大学, 医学(系)研究科(研究院), 教授 (20423824)
MIYAZAKI Tomoyuki 横浜市立大学, 医学部, 助教 (30580724)
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Research Collaborator |
TOMINAGA Yosuke
ASAKURA Ayako
YUBA Yuki
YONEZAKI Kumiko
ADACHI Akiko
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Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 吸入麻酔薬 / 記憶学習 / 海馬 / 受動回避 / 神経可塑性 / 長期増強 / AMPA型グルタミン酸受容体 / 静脈麻酔薬 / グルタミン酸受容体 / 電気生理学 / 忌避刺激 |
Outline of Final Research Achievements |
General anesthesia induces long-lasting cognitive and learning deficits. However, the underlying mechanism remains unknown. The GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a key molecule for learning and synaptic plasticity, which requires trafficking of GluA1-containing AMPARs into the synapse. Seven days after exposure to 1.8% isoflurane for 2 h (Iso1.8), the inhibitory avoidance learning (P = 0.002) and long-term potentiation (P < 0.001) were impaired, however, propofol-administrationed model was not impaired (P = 0.14). Iso1.8 also temporarily increased GluA1 in the synaptoneurosomes (P = 0.012) and reduced the GluA1 ubiquitination, a main degradation pathway of GluA1 (P = 0.014). Isoflurane impairs hippocampal learning and modulates synaptic plasticity in the postanesthetic period, in contrast to propofol administration. Increased GluA1 may reduce synaptic capacity for additional GluA1-containing AMPARs trafficking.
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Report
(4 results)
Research Products
(7 results)