The effect of sevoflurane anesthesia on learning and memory and hippocampal histone acetylation in mice

Abstract

Objective To investigate the effect of sevoflurane anesthesia on learning and memory in mice and the relationship with histone acetylation. Methods Thirty-six adult male C57BL/6 mice were randomly divided into control group(mice inhaled 95% O2 for 6 h), sevoflurane (Sevo) group (1.5% Sevo group, 2% Sevo group, 3% Sevo group: mice inhaled 1.5%, 2% and 3% sevoflurane for 6 h respectively), sevoflurane + SAHA (Sevo + SAHA) group (mice were intraperitoneally injected with histone deacetylase inhibitor SAHA (25 mg/kg). And 1 h later, 3% Sevo was inhaled continuously for 6 hours.)and SAHA group(mice were intraperitoneally injected with histone deacetylase inhibitor SAHA (25 mg/kg)). The ability of learning and memory in mice was estimated by Morris water maze. The expression levels of Ac-H3, BDNF and Syt-I protein in the hippocampus were detected by Western blot. Results In Morris water maze, 3% sevoflurane anesthesia significantly prolonged the escape latency((46.91±1.84)s), and significantly decreased the ratio of target time((35.84±5.40)%) compared with that of control group((23.46±2.67)s, (49.74±4.91)%, P<0.05). Compared with 3% Sevo group, the ratio of target time in Sevot+ SAHA group((46.86±4.37)%) was increased(P<0.05). Moreover, 3% sevoflurane anesthesia significantly decreased the expression levels of Ac-H3 (10.23±2.45), BDNF (6.72±1.21) and Syt-I (8.25±2.11) in the hippocampus compared with that of control group((15.45±2.58), (10.17±1.45) and (15.02±3.38), P<0.05). However, pre-administration of the histone deacetylase inhibitor SAHA significantly increased the ratio of target time in Morris water maze, and improved the expression levels of Ac-H3 (14.06±2.79), BDNF (10.13±1.06) and Syt-I (14.16±3.66) in Sevo+ SAHA group compared with that of Sevo group (P<0.05). Conclusion The high dose of sevoflurane anesthesia can induce learning and memory impairment through the inhibitation of histone acetylation in the hippocampus. Key words: Sevoflurane; Histone acetylation; Learning and memory