小剂量艾司氯胺酮对慢性睡眠剥夺大鼠学习记忆功能的影响及海马AMPAR在其中的作用
Effect of small-dose esketamine on learning and memory ability of chronic sleep-deprived rats and role of hippocampal AMPAR
杨丽丽 1张晓爽 1解雅英1
作者信息
- 1. 内蒙古医科大学附属医院麻醉科,呼和浩特 010010
- 折叠
摘要
目的 评价小剂量艾司氯胺酮对慢性睡眠剥夺大鼠学习记忆功能的影响及海马α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)在其中的作用.方法 健康雄性SD大鼠40只,体质量200～280 g,4月龄,采用随机数字表法分为4组(n=10):正常对照组(N组)、慢性睡眠剥夺组(SD组)、慢性睡眠剥夺+艾司氯胺酮组(SDK组)和慢性睡眠剥夺+艾司氯胺酮+AMPAR拮抗剂CNQX组(SDKI组).采用改良水平台环境法制备睡眠剥夺模型.造模结束后连续3 d,SDK组腹腔注射艾司氯胺酮10 mg/kg,SDKI组腹腔注射CNQX 1 mg/kg后注射艾司氯胺酮10 mg/kg.睡眠剥夺结束或给药后采用Morris水迷宫实验检测空间学习记忆功能.水迷宫实验结束后,处死大鼠,取海马组织,采用qPCR法检测海马Homer1a mRNA表达,Western blot法检测海马Homer1a、代谢型谷氨酸受体5(mGluR5)和AMPAR的表达;高尔基染色法检测海马CA1区树突棘密度.结果 与N组比较,SD组逃避潜伏期延长,目标象限停留时间百分比及穿越原平台位置次数减少,海马Homer1a及其mRNA、mGluR5表达上调,AMPAR表达下调,CA1区树突棘密度减少(P＜0.05);与SD组比较,SDK组逃避潜伏期缩短,目标象限停留时间百分比及穿越原平台位置次数增加,海马AMPAR表达上调,CA1区树突棘密度增加(P＜0.05);与SDK组比较,SDKI组逃避潜伏期延长,目标象限停留时间百分比及穿越原平台位置次数减少,海马AMPAR表达下调,CA1区树突棘密度减少(P＜0.05).SD组、SDK组和SDKI组海马Homer1a及其mRNA、mGluR5表达比较差异无统计学意义(P＞0.05).结论 小剂量艾司氯胺酮可改善慢性睡眠剥夺大鼠的学习记忆功能,机制可能与上调海马AMPAR表达有关.
Abstract
Objective To evaluate the effect of small-dose esketamine on the learning and memory ability of chronic sleep-deprived rats and the role of hippocampal amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors(AMPARs).Methods Forty healthy male Sprague-Dawley rats,aged 4 months,weighing 200-280 g,were divided into 4 groups(n=10 each)using a random number table method:nor-mal control group(N group),chronic sleep deprivation group(SD group),chronic sleep deprivation+es-ketamine group(SDK group)and chronic sleep deprivation+esketamine+AMPAR antagonist CNQX group(SDKI group).The sleep deprivation model was prepared by the modified multi-platform water environment method.For 3 consecutive days after developing the model,ketamine 10 mg/kg was intraperitoneally injected in SDK group,and SDKI group received intraperitoneal injection of CNQX 1 mg/kg followed by ketamine 10 mg/kg.Morris water maze test was used to detect spatial learning and memory ability after the end of sleep deprivation or after administration.After the water maze test,rats were sacrificed,and the hippocampal tis-sue was obtained to detect the expression of hippocampal Homer1a mRNA(by quantitative polymerase chain reaction),Homer1a,metabotropic glutamate receptor 5(mGluR5)and AMPAR(by Western blot).The density of dendritic spines in hippocampal CA1 region was determined by Golgi staining.Results Com-pared with N group,the escape latency was significantly prolonged,the percentage of time spent in the tar-get quadrant and the number of times the animals crossing the platform were decreased,the expression of Homer1a protein and mRNA and mGluR5 was up-regulated,the expression of AMPAR was down-regulated,and the density of dendritic spines in hippocampal CA1 region was decreased in SD group(P＜0.05).Com-pared with SD group,the escape latency was significantly shortened,the percentage of time spent in the tar-get quadrant and the number of times the animals crossing the platform were increased,the expression of AMPAR was up-regulated,and the density of dendritic spines in hippocampal CA1 region was increased in SDK group(P＜0.05).Compared with SDK group,the escape latency was significantly prolonged,the per-centage of time spent in the target quadrant and the number of times the animals crossing the platform were decreased,the expression of AMPAR was down-regulated,and the density of dendritic spines in hippocam-pal CA1 region was decreased in SDKI group(P＜0.05).There was no significant difference in the expres-sion of Homer1a protein and mRNA and mGluR5 among SD group,SDK group and SDKI group(P＞0.05).Conclusions Small-dose esketamine can improve the learning and memory ability of chronic sleep-deprived rats,and the mechanism may be related to up-regulation of the expression of hippocampal AMPARs.
关键词
睡眠剥夺/认知功能障碍/受体,AMPA/艾司氯胺酮Key words
Sleep deprivation/Cognitive dysfunction/Receptors,AMPA/Esketamine引用本文复制引用
出版年
2024
NETL
NSTL
万方数据