Effects of Sevoflurane on Young Male Adult C57BL/6 Mice Spatial Cognition.
Inhalation anesthetics are reported to affect cognition in both animals and humans. The influence of inhalation anesthetics in learning and memory are contradictory. We therefore investigated the effects of sevoflurane anesthesia with different durations on cognitive performance and the levels of NMDA receptor subunit NR2B, phosphorylated ERK1/2 (p-ERK1/2) and activated caspase3 in mouse hippocampus. We anaesthetized eight-week old male C57BL/6 mice with 2.5% sevoflurane for durations ranging from one to four hours. Non-anaesthetized mice served as controls. Mice exposed to sevoflurane for one to three hours showed improved performance, whereas mice with exposure up to four hours displayed similar behavioral performance as control group. NR2B was increased both at 24h and at two weeks post sevoflurane exposure in all groups. The p-ERK1/2: total ERK1/2 ratio increased at 24h in all anesthesia groups. The ratio remained elevated at two weeks in groups with two- to four-hour exposure. Activated caspase3 was detected elevated at 24h in groups with two- to four-hour exposure. The elevated trend of activated caspase3 was still detectable at two weeks in groups with three- to four-hour exposure. At two weeks post anesthesia, the typical morphology associated with apoptotic cells was observed in the hippocampus of mice exposed to four hours of sevoflurane. Our results indicate that 2.5% sevoflurane exposure for one to three hours improved spatial cognitive performance in young adult mice. The cognitive improvement might be related to the increase of NR2B, the p-ERK1/2: total ERK1/2 ratio in hippocampus. However, exposure to sevoflurane for four hours caused neurotoxicity due to caspase3 activation and apoptosis.
Department of Anesthesiology, Tongji Hospital affiliated Tongji University, Shanghai, China.
Jianhui
J
Liu
Department of Anesthesiology, Tongji Hospital affiliated Tongji University, Shanghai, China.
Xiaoqing
X
Zhang
Department of medical image, Tongji Hospital affiliated Tongji University, Shanghai, China.
Wei
W
Zhang
Department of medical image, Tongji Hospital affiliated Tongji University, Shanghai, China.
Guojun
G
Gu
Department of medical image, Tongji Hospital affiliated Tongji University, Shanghai, China.
Peijun
P
Wang
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000077149:Sevoflurane; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D000777:Anesthetics; D008738:Methyl Ethers; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000077149:Sevoflurane; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3