The effect of sevoflurane anesthesia on learning and memory and hippocampal histone acetylation in mice / 中华行为医学与脑科学杂志

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 ran-domly divided into control group(mice inhaled 95％ O2 for 6 h), sevoflurane (Sevo) group (1. 5％ Sevo group, 2％ Sevo group, 3％ Sevo groupmice 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 abil-ity 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 hippo-campus 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 ra-tio 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.