title: Voluntary exercise rescues sevoflurane-induced memory impairment in aged male mice.
abstract: Postoperative cognitive impairment is especially common in older patients following major surgery. Although exposure to sevoflurane is known to cause memory deficits, few studies have examined the putative approaches to reduce such impairments. This study tested the hypotheses that sevoflurane exposure can decrease NR2B subunit-containing NMDA receptor activity in hippocampus of aged mice, and voluntary exercise may counteract the declining hippocampal functions. We found that long exposure (3 h/day for 3 days), but not short exposure (1 h/day for 3 days), to 3 % sevoflurane produced a long-lasting spatial memory deficits up to 3 weeks in aged mice, and such an effect was not due to the neuronal loss in the hippocampus, but was correlated with a long-term decrease in Fyn kinase expression and NR2B subunit phosphorylation in the hippocampus. Furthermore, voluntary exercise rescued sevoflurane-induced spatial memory deficits in aged mice and restored Fyn kinase expression and NR2B subunit phosphorylation in the hippocampus to a level comparable to control animals. Generally, our results suggested that Fyn-mediated NR2B subunit phosphorylation may play a critical role in sevoflurane-induced impairment in cognitive functions in aged animals, and voluntary exercise might be an important non-pharmacological approach to treatment of inhaled anesthetics-induced postoperative cognitive impairment in clinical settings.
authors.affiliation: Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Gynecology, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, China. jinlongli1978@gmail.com.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects; D005081:Exercise Therapy / Q000379:methods*; D006624:Hippocampus / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000534:rehabilitation*; D008738:Methyl Ethers / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018685:Anesthetics, Inhalation; C491468:Fyb protein, mouse; D008738:Methyl Ethers; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000077149:Sevoflurane
keywords: Hippocampus; NR2B subunit; Sevoflurane; Spatial memory; Voluntary exercise