Effect of ketamine on expression of hippocampal microRNA-206 in mentally depressed rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of ketamine on the expression of hippocampal microRNA-206 (miR-206) in the mentally depressed rats.Methods Eighty healthy female Sprague-Dawley rats,weighing 200-300 g,aged 2-3 months,were randomly divided into 4 groups (n=20 each) using a random number tablenormal control group (C group),ketamine group (K group),depression group (D group) and depression + ketamine group (D+K group).Mental depression was induced by exposing the animal to chronic unpredictable mild stress.At 1 day after successful establishment of the model,ketamine 15 mg/kg was injected intraperitoneally in K and D+K groups,while the equal volume of normal saline was given in C and D groups.Before establishment of thc model,at 7,14,21,28 and 35 days after beginning of establishment of the model,and at 1,3,5 and 7 days after administration,sucrose preference test was performed.Open field test was carried out at 1 day after administration.Forced swimming test was performed at 2 days after administration.Five rats were sacrificed at 6 h after administration,and hippocampal tissues were isolated for determination of the expression of hippocampal miR-206 by quantitative real-time polymerase chain reaction.At 2 days after administration,5 rats were sacrificed,and hippocampal brain-derived neurotrophic factor (BDNF) expression was detected by Western blot.Results Compared with C group,the volume of sucrose intake at 21-35 days after beginning of establishment of the model and at each time point after administration and the score of open field test were significantly decreased,the immobility time in forced swimming test was significantly prolonged,the expression of miR206 was up-regulated,and the expression of BDNF was down-regulated in D group,the immobility time in forced swimming test was shortened,the expression of miR-206 was down-regulated,and the expression of BDNF was up-regulated in group K,and the score of open field test and volume of sucrose intake at 21-35days after beginning of establishment of the model and the score of open field test were significantly decreased in D+K group (P＜0.05).Compared with D group,the volume of sucrose intake at each time point after administration was significantly increased,the immobility time in forced swimming test was shortened,the expression of miR-206 was down-regulated,and the expression of BDNF was up-regulated in D+K group (P＜0.05).Conclusion The mechanism by which ketamine exerts antidepressant effects is related to down-regulation of miR-206 expression and up-regulation of BDNF expression in the hippocampus of rats.