Is there any difference in the effects of sevoflurane inhalation on hippocampal neuronal phosphorylated cAMP response element-binding protein between male and female rats

Abstract

Objective To investigate the difference in the effects of sevoflurane inhalation on hippocampal neuronal phosphorylated cAMP response element-binding protein between male and female rats.Methods Fiftyeight healthy SD rats aged 3 months weighing 180-440 g were randomly divided into 4 groups:group female control (Fc group,n ＝ 15) ; group female sevoflurane (Fs group,n ＝ 15) ; group male control (Mc group,n ＝ 14) and group male sevoflurane (Ms group,n ＝ 14).The 2 control groups (Fc group,Mc group) inhaled 95％ 02 for 2 h,while the 2 sevoflurane groups (Fs group,Ms group) inhaled 3％ sevoflurane for 2 h.The cognitive function was assessed by passive avoidance task performed on the 2nd day after sevoflurane inhalation and Morris water maze test once a day for 5 consecutive days from day 3-7 after sevoflurane.The animals were sacrificed after last cognitive function assessment test on the 7th day after sevoflurane inhalation and their brains were removed for determination of expression of hippocampal neuronal p-CREB1,Bcl-2 and caspase-8 protein expression.Results Sevoflurane inhalation significantly increased the escape latency and swimming distance at day 3 after sevoflurane inhalation in group Fs and at days 3-6 in group Ms as compared with their control groups (Fc group,Mc group) in Morris water maze test.The escape latency and swimming distance were significantly longer at 4-6 d in Ms group than in Fs group.Sevoflurane significantly decreased p-CREB1 and Bcl-2 protein expression and increased caspase-8 expression in groups Fs and Ms as compared with their control groups (Fc group,Mc group).Bcl-2 protein expression was significantly higher in group Fs than in group Ms.Conclusion Two hour 3 ％ sevoflurane inhalation can induce hippocampal neuronal apoptosis by down-regulating CREB1 phosphorylation and Bcl-2 expression and up-regulating caspase-8 expression.The effects are greater in male rats than in female rats. Key words: Anesthetics,inhalation; Sex factors; Cyclic AMP response element-binding protein; Hippocampus ; Neurons