Ketamine alleviating depressive-like behaviors is associated with regulation of nNOS-CAPON-Dexras1 complex in chronic unpredictable mild stress rats

作者全名："Shen, Yiwei; Lv, Feng; Min, Su; Hao, Xuechao; Yu, Jian"

作者地址："[Shen, Yiwei; Lv, Feng; Min, Su; Hao, Xuechao; Yu, Jian] Chongqing Med Univ, Dept Anesthesiol, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Min, S (通讯作者)，Chongqing Med Univ, Dept Anesthesiol, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：TRANSLATIONAL NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000857949500001

JCR分区：Q4

影响因子：2.1

年份：2022

卷号：13

期号：1

开始页：309

结束页：319

文献类型：Article

关键词：ketamine; depression; neuronal nitric oxide synthase; CAPON protein; Dexras1 protein

摘要："Background A growing number of studies have demonstrated that ketamine induces rapid and sustained antidepressant action. Neuronal nitric oxide synthase (nNOS) signaling has been explored for the treatment of neuropsychiatric disorders for decades. But the effect of ketamine on nNOS signaling is poorly understood. The aim of the present study was to investigate the effect of ketamine on nNOS signaling in a chronic unpredictable mild stress (CUMS) model of depression. Methods Forty-eight rats were randomly divided into four groups: the control group of healthy rats (group C), the healthy rats treated with ketamine 10 mg/kg for 3 days (group CK), the rats model of stress-induced depression group (group D), and the depressed group treated with ketamine 10 mg/kg for 3 days (group DK). The sucrose preference test and open field test were used to assess behavioral changes. Immunohistochemistry, immunofluorescence, and real-time PCR analysis were carried out to measure the expression of nNOS, CAPON, and Dexras1 in the prefrontal cortex (PFC) of the CUMS rats. Results Compared with healthy rats, the total distance traveled, the rearing counts, the sucrose preference percentage (SPP), and CAPON and Dexras1 expression in the PFC significantly decreased, while nNOS expression increased in CUMS rats. After treating with ketamine, the total distance traveled, the rearing counts, the SPP, and CAPON and Dexras1 expression significantly increased, while nNOS expression significantly decreased. Conclusion The results indicated that ketamine improved the depressive behavior of rats, which may be related to the reduced nNOS expression and enhanced CAPON and Dexras1 expression."

基金机构：National Natural Science Foundation of China [81901377]; Chongqing Social Science Planning Project [2021NDQN55]; ERAS in Chongqing [2018-MZ-2]

基金资助正文："This work has received funding from the National Natural Science Foundation of China grant (No. 81901377) and the Chongqing Social Science Planning Project (2021NDQN55), and also received support from the Xinchen Cup Cultivation Project of peri-operative Anesthesia and ERAS in Chongqing (2018-MZ-2)."