Effect of small-dose esketamine on learning and memory ability of chronic sleep-deprived rats and role of hippocampal AMPAR
10.3760/cma.j.cn131073.20231030.00417
- VernacularTitle: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
- Author:
Lili YANG
1
;
Xiaoshuang ZHANG
;
Yaying XIE
Author Information
1. 内蒙古医科大学附属医院麻醉科，呼和浩特 010010
- Keywords:
Sleep deprivation;
Cognitive dysfunction;
Receptors, AMPA;
Esketamine
- From:
Chinese Journal of Anesthesiology
2024;44(4):466-470
- CountryChina
- Language:Chinese
-
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: normal control group (N group), chronic sleep deprivation group (SD group), chronic sleep deprivation+ esketamine 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 tissue 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:Compared with N group, the escape latency was significantly prolonged, the percentage of time spent in the target 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). Compared with SD group, the escape latency was significantly shortened, the percentage of time spent in the target 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 percentage 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 hippocampal CA1 region was decreased in SDKI group ( P<0.05). There was no significant difference in the expression 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.
