Role of hippocampal α7nAChR in sevoflurane-induced deficit in long-term cognitive function in neonatal rats

Abstract

Objective To investigate the role of hippocampal α7 nicotinic acetylcholine receptor (α7nAChR) in sevoflurane-induced deficit in long-term cognitive function in neonatal rats.Methods Sixty-four male Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were randomly divided into 4 groups (n =16each) using a random number table:control group (group C),sevoflurane anesthesia group (group S),sevoflurane anesthesia + α7nAChR agonist PNU-282987 group (group PS),and α7nAChR inhibitor MLA group (group M).In C and S groups,the rats inhaled 30％ oxygen and 3％ sevoflurane for 6 h,respectively.In group PS,PNU282987 (5 mg/kg) was injected intraperitoneally and 24 h later the rats were exposed to 3％ sevoflurane for 6 h.In group M,MLA 3 mg/kg was injected intrappritoneally and 24 h later the rats inhaled 30％ oxygen for 6 h.Eight rats in each group were randomly chosen and sacrificed immediately after oxygen or sevoflurane inhalation.The hippocampus was renoved for determination of the expression of α7nAChR and NR1,NR2A and NR2B subunitscontaining NMDA receptors in the total protein and membrane protein in hippocampal neurons.When the left rats in each group were raised to 2 months,Y-maze test was performed to detect the cognitive function.Results Compared with group C,the expression of α7nAChR and NR1,NR2A and NR2B subunits-containing NMDA receptors in the membrane protein was significantly down-regulated,and the percentage of spontaneous alternation was decreased in group S,the expression of NRI and NR2A subunits-containing NMDA receptors in the membrane protein was down-regulated (P ＜ 0.05),and no significant change was found in the expression of NR2B subunitscontaining NMDA receptors in the membrane protein and percentage of spontaneous alternation in group PS (P ＞ 0.05),and no significant change was found in the expression of NR1 and NR2A subunits-containing NMDA receptors in the membrane protein (P ＞ 0.05),and the expression of NR2B subunits-containing NMDA receptors in the membrane protein was down-regulated,and the percentage of spontaneous alternation was decreased in group M (P ＜ 0.05).Compared with group S,no significant change was found in the expression of NR1 and NR2A subunits-containing NMDA receptors in the membrane protein (P ＞ 0.05),and the expression of NR2B subunitscontaining NMDA receptors in the membrane protein was significantly up-regulated,and the percentage of spontaneous alternation was increased in PS group (P ＜ 0.05).There was no significant difference in the expression of α7nAChR and NR1,NR2A and NR2B subunits-containing NMDA receptors in the total protein and the number of entries into each arm in Y-maze test between the four groups (P ＞ 0.05).Conclusion The mechanism by which sevoflurane induces deficit in long-term cognitive function may be related to decreased function of hippocampal α7nAChR and inhibition of function of NMDA receptors in neonatal rats. Key words: Receptors, nicotinic; Anesthetics, inhalation; Infant, newborn; Child development; Cognition disorders; Hippocampus