Increased extrasynaptic GluN2B expression is involved in cognitive impairment after isoflurane anesthesia.
Increased extrasynaptic GluN2B expression is involved in cognitive impairment after isoflurane anesthesia.
复制标题
突触外 GluN2B 表达增加与异呋喃麻醉后认知障碍有关
DOI：
10.3892/etm.2016.3306
复制
发表时间：
2016-07
影响因子：
2.7
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Li L;Li Z;Cao Y;Fan D;Chui D;Guo X
老年人术后认知功能障碍(POCD)越来越受到人们的关注，全麻药被认为与其有关。异氟醚暴露诱导麻醉后N-甲基-D-天冬氨酸受体(NMDAR)GluN2B亚单位表达增加，并伴有认知功能的改变。然而，异氟醚是否在不同的亚细胞室中影响这种表达，并参与POCD的发展仍有待阐明。本研究旨在探讨异氟醚对老年大鼠突触和突触外NMDAR亚单位GluN2A和GluN2B表达的影响及其对认知功能的影响。GluN2B拮抗剂Ro25-6981被给予异氟醚暴露的大鼠，以确定GluN2B在异氟烷诱导的认知功能改变中的作用。结果表明，异氟醚暴露后至少7d，Morris水迷宫(MWM)大鼠的空间学习记忆能力受到损害，30d后恢复到对照水平。Ro25-6981治疗可以减轻这种损害。与非异氟醚暴露相比，异氟醚暴露后突触外GluN2B蛋白的表达显著增加，但突触GluN2B或GluN2A蛋白的表达没有显著增加，并在大约30天后恢复到对照水平。本研究结果表明，异氟醚可诱导麻醉后突触外GluN2B表达的持续上调，并参与可逆性认知损害。
There is increasing concern regarding the postoperative cognitive dysfunction (POCD) in the aging population, and general anesthetics are believed to be involved. Isoflurane exposure induced increased N-methyl-D-aspartic acid receptor (NMDAR) GluN2B subunit expression following anesthesia, which was accompanied by alteration of the cognitive function. However, whether isoflurane affects this expression in different subcellular compartments, and is involved in the development of POCD remains to be elucidated. The aims of the study were to investigate the effects of isoflurane on the expression of the synaptic and extrasynaptic NMDAR subunits, GluN2A and GluN2B, as well as the associated alteration of cognitive function in aged rats. The GluN2B antagonist, Ro25–6981, was given to rats exposed to isoflurane to determine the role of GluN2B in the isoflurane-induced alteration of cognitive function. The results showed that spatial learning and memory tested in the Morris water maze (MWM) was impaired at least 7 days after isoflurane exposure, and was returned to control levels 30 days thereafter. Ro25-6981 treatment can alleviate this impairment. Extrasynaptic GluN2B protein expression, but not synaptic GluN2B or GluN2A, increased significantly after isoflurane exposure compared to non-isoflurane exposure, and returned to control levels approximately 30 days thereafter. The results of the present study indicated that isoflurane induced the prolonged upregulation of extrasynaptic GluN2B expression after anesthesia and is involved in reversible cognitive impairment.