General anesthesia impairs learning via the saturation of synaptic plasticity.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• 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)
• Research Collaborator: TOMINAGA Yosuke ; ASAKURA Ayako ; YUBA Yuki ; YONEZAKI Kumiko ; ADACHI Akiko
• Project Period (FY): 2012-04-01 – 2015-03-31
• 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

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.

Free Research Field

生体制御・麻酔科学