title: Increased extrasynaptic GluN2B expression is involved in cognitive impairment after isoflurane anesthesia.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Lunxu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Zhengqian
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fan
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Peking University Health Science Center, Beijing 100083, P.R. China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Chui
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Guo
keywords: N-methyl-D-aspartic acid receptor; cognitive impairment; extrasynaptic GluN2B; isoflurane