Voluntary exercise rescues sevoflurane-induced memory impairment in aged male mice

• Published in: Experimental brain research 2016-12, Vol.234 (12), p.3613-3624
• Main Authors: Tian, Dan, Tian, Miao, Ma, Zhiming, Zhang, Leilei, Cui, Yunfeng, Li, Jinlong
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Analysis of Variance; Anesthetics, Inhalation - adverse effects; Animal cognition; Animals; Biomedical and Life Sciences; Biomedicine; Brain research; Cognitive ability; Disease Models, Animal; Escape Reaction - drug effects; Exercise; Exercise Therapy - methods; Health aspects; Hippocampus - pathology; Laboratory animals; Male; Maze Learning - drug effects; Memory; Memory disorders; Memory Disorders - blood; Memory Disorders - chemically induced; Memory Disorders - pathology; Memory Disorders - rehabilitation; Methyl Ethers - adverse effects; Mice; Mice, Inbred C57BL; Neurology; Neurons - metabolism; Neurons - radiation effects; Neurosciences; Phosphorylation; Postoperative complications; Prevention; Reaction Time - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Research Article; Sevoflurane; Surgery; Time Factors
• ISSN: 0014-4819; 1432-1106
• DOI: 10.1007/s00221-016-4756-8

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.