Effect of esketamine on learning and memory function after chronic stress and hippocampal NMDAR-CaMK Ⅱ-CREB signaling pathway in developing rats
10.3760/cma.j.cn131073.20231011.00320
- VernacularTitle:艾司氯胺酮对发育期大鼠慢性应激后学习记忆功能及海马NMDAR-CaMKⅡ-CREB信号通路的影响
- Author:
Guiping XU
1
;
Xuexue ZHANG
;
Yang WANG
;
Yuxuan ZHANG
Author Information
1. 新疆维吾尔自治区人民医院麻醉科 新疆麻醉管理临床医学研究中心，乌鲁木齐 830000
- Keywords:
Cognition;
Receptors, N-methyl-D-aspartate;
Calcium-calmodulin-dependent protein kinase type 2;
Cyclic AMP response element-binding protein;
Chronic stres
- From:
Chinese Journal of Anesthesiology
2024;44(3):353-357
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of esketamine on learning and memory function after chronic stress and the signaling pathway of N-methyl-D-aspartate receptor (NMDAR)-calmodulin-dependent protein kinase type 2 (CaMKⅡ)-cAMP-responsive element-binding protein (CREB) in the hippocampus of developing rats.Methods:Sixty clean-grade healthy Sprague-Dawley rats of either sex, aged 7 days, weighing 10-15 g, were divided into 3 groups ( n=20 each) using a random number table method: control+ normal saline group (CN group), chronic stress+ normal saline group (NS group), and chronic stress+ esketamine group (ES group). A chronic stress model was established using a chronic unpredictable stress method. After the end of stress stimulation, esketamine 10 mg/kg was intraperitoneally injected once a day for 7 consecutive days in ES group, and the equal volume of normal saline was given instead in NS group. Y maze test and Morris water maze test were used to assess the learning and memory function after intraperitoneal administration. Venous blood samples were obtained to measure the serum cortisol and reactive oxygen species (ROS) concentrations by enzyme-linked immunosorbent assay. The animals were then sacrificed under anesthesia, the brain was removed and the hippocampal tissue was isolated for examination of the pathological changes in the hippocampal CA1 region and for determination of the ratios of phosphorylated NMDAR (p-NMDAR)/NMDAR, phosphorylated CaMKII (p-CaMKⅡ)/CaMKⅡ, and phosphorylated CREB (p-CREB)/CREB (by Western blot). Results:Compared with CN group, the time spent in the novel arm was significantly shortened, the number of entries into the novel arm was reduced, the escape latency was prolonged, the number of crossing the original platform was reduced, the serum cortisol and ROS concentrations were increased, the p-NMDAR/NMDAR ratio, p-CaMKⅡ/CaMKⅡ ratio and p-CREB/CREB ratio were decreased ( P<0.05), and the pathological changes of neurons were marked in NS group. Compared with NS group, the time spent in the novel arm was significantly prolonged, the number of entries into the novel arm was increased, the escape latency was shortened, the number of crossing the original platform was increased, the serum cortisol and ROS concentrations were decreased, the p-NMDAR/NMDAR ratio, p-CaMKⅡ/CaMKⅡ ratio and p-CREB/CREB ratio were increased ( P<0.05), and the pathological changes of neurons were significantly attenuated in ES group. Conclusions:Esketamine can improve the learning and memory function after chronic stress in developing rats, and the mechanism may be related to reduction of oxidative stress and enhancement of the activity of hippocampal NMDAR-CaMKII-CREB signaling pathway.
