Role of autophagy in hippocampal neurons in cognitive dysfunction caused by sevoflurane anesthesia in juvenile rats

Abstract

Objective To evaluate the role of autophagy in hippocampal neurons in cognitive dysfunction caused by sevoflurane anesthesia in juvenile rats. Methods One hundred four male Sprague-Dawley rats, aged 7 days, weighing 10-16 g, were randomly assigned into 3 groups using a random number table: control group(group C, n=8), sevoflurane anesthesia group(group S, n=48), and sevoflurane anesthesia + rapamycin group(group SR, n=48). Group C inhaled 60% oxygen for 6 h. S and SR groups inhaled 3.6% sevoflurane anesthesia for 6 h, and in addition, rapamycin 2 mg/kg was injected intraperitoneally at 1 h before of sevoflurane inhalation in group SR.The equal volume of phosphate buffer solution was given in C and S groups.At 1 h before sevoflurane anesthesia(T0), immediately after the end of anesthesia(T1), and at 12, 24 and 48 h after the end of anesthesia(T2-4), 8 rats were randomly selected from S and SR groups to determine the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3(LC3)Ⅰ, LC3Ⅱ and Beclin-1 in hippocampal neurons(by Western blot). The ratio of LC3Ⅱ/LC3Ⅰ was calculated.Morris water maze test was performed at 5 weeks after the end of anesthesia to assess the cognitive function.The escape latency, frequency of crossing the original platform, and duration of swimming spent at the target quadrant were recorded. Results Compared with the values at T0, the expression of LC3Ⅱ and Beclin-1 was significantly down-regulated at T1-3, and the ratio of LC3Ⅱ/LC3Ⅰ was decreased in group S, and the expression of LC3Ⅱ and Beclin-1 was significantly up-regulated at T1-4, and the ratio of LC3Ⅱ/LC3Ⅰ was increased in group SR(P 0.05). Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, and the duration of swimming spent at the target quadrant was prolonged at 3-5 days, the expression of LC3Ⅱ and Beclin-1 was up-regulated at T1-4, and the ratio of LC3Ⅱ/LC3Ⅰ was increased in group SR(P<0.05). Conclusion Weakened autophagy in hippocampal neurons is involved in cognitive dysfunction caused by sevoflurane anesthesia in the juvenile rats. Key words: Anesthetics, inhalation; Cognition disorders; Autophagy; Hippocampus; Child