Ketamine alleviates PTSD-like effect and improves hippocampal synaptic plasticity via regulation of GSK-3(3/GR (3 /GR signaling of rats
文献类型：期刊论文
| 作者 | Wang, Zixun12,13,14; Hu, Xinyu10,11; Wang, Zhongyi9,14; Chen, Jiaming14; Wang, Ling8; Li, Changjiang11; Deng, Jing7; Yue, Kuitao5,6; Wang, Lizhuo4; Kong, Yujia3 |
| 刊名 | JOURNAL OF PSYCHIATRIC RESEARCH
 |
| 出版日期 | 2024-10-01 |
| 卷号 | 178页码:259-269 |
| 关键词 | PTSD Ketamine Synaptic plasticity GSK-3(3 GR |
| ISSN号 | 0022-3956 |
| DOI | 10.1016/j.jpsychires.2024.08.019 |
| 通讯作者 | Sun, Lin(linsun2013@sdsmu.edu.cn) |
| 英文摘要 | Background: Each year, 3-4% of the global population experiences post-traumatic stress disorder (PTSD), a chronic mental disorder with significant social and economic repercussions. Although it has been shown that ketamine can effectively alleviate PTSD symptoms in individuals, the specific mechanism of action underlying its anti-PTSD effects remains unclear. In this study, we investigated how a single, low dose of ketamine affected the glycogen synthase kinase 3(3 (GSK-3(3)/glucocorticoid receptor (GR) signaling pathway in a single prolonged stress (SPS)-induced PTSD rat model. Methods: After establishing the model, stress-related behavioral alterations in the rats were assessed following intraperitoneal injections of ketamine (10 mg/kg) and GSK-3(3 antagonist SB216763 (5 mg/kg). In the hippo- campus, alterations in the expression of specific proteins implicated in PTSD development, such as GR, brain- derived neurotrophic factor (BDNF), GSK-3(3, and phosphorylated glycogen synthase kinase 3(3 (p-GSK-3(3), were assessed. We also measured changes in the mRNA expression levels of GR, BDNF, GSK-3(3, FK501 binding protein 51 (FKBP5), and corticotropin-releasing hormone (CRH), as well as synaptic ultrastructure, in the hippocampus, and measured changes in corticosterone levels in the blood. Results: SPS induced anxiety-like and depression-like behaviors in rats and induced morphological changes in synapse, which were accompanied by higher GSK-3(3 protein expression and conversely, decreased expression of GR, BDNF, p-GSK-3(3, FKBP5 and CRH. Intraperitoneal administration of ketamine (10 mg/kg) after SPS prevented SPS-induced anxiety-like behaviors. Most importantly, ketamine attenuated SPS-induced dysfunctions in GSK-3(3/GR signaling and synaptic deficits. Furthermore, treatment with a GSK-3(3 inhibitor played the same effect as ketamine on behavioral changes of SPS model rats. Conclusion: Single doses of ketamine effectively ameliorate SPS-induced anxiety-like symptoms, potentially by improving synaptic plastic in the hippocampus by regulating GSK-3(3/GR signaling. |
| 收录类别 | SCI |
| WOS关键词 | GLYCOGEN-SYNTHASE KINASE-3-BETA ; STRESS ; MODELS |
| 资助项目 | National Nature Science Foundation of China (NSFC)[82101588] ; National Nature Science Foundation of China (NSFC)[200033560] ; Education and Teaching Reform Project of the Psychology and Education Reference Committee of the Ministry of Education[20221013] ; Institute of Psychology, Chinese Academy of Sciences[GJ202002] ; Surface Project of Natural Science Foundation of Shandong Province[ZR2020MC218] ; Science and Technology Development Program in Weifang City[2021YX042] ; Science and Technology Development Program in Weifang City[2022GX011] |
| WOS研究方向 | Psychiatry |
| 语种 | 英语 |
| WOS记录号 | WOS:001299687300001 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 资助机构 | National Nature Science Foundation of China (NSFC) ; Education and Teaching Reform Project of the Psychology and Education Reference Committee of the Ministry of Education ; Institute of Psychology, Chinese Academy of Sciences ; Surface Project of Natural Science Foundation of Shandong Province ; Science and Technology Development Program in Weifang City |
| 源URL | [http://ir.psych.ac.cn/handle/311026/48827]  |
| 专题 | 心理研究所_中国科学院心理健康重点实验室 |
| 通讯作者 | Sun, Lin |
| 作者单位 | 1.Univ Chinese Acad Sci, Dept Psychol, Beijing 100049, Peoples R China 2.Shanting Dist Peoples Hosp, Dept Neurosurg, Beijing Rd, Zaozhuang 277200, Shandong, Peoples R China 3.Management Comm Shanting Econ Dev Zone, 37 Fuqian Rd, Zaozhuang 277200, Shandong, Peoples R China 4.Shandong Second Med Univ, Sch Publ Hlth, 7166 Baotong West St, Weifang 261053, Shandong, Peoples R China 5.Peoples Hosp Shanting Dist Zaozhuang, Zaozhuang 277200, Shandong, Peoples R China 6.Shandong Second Med Univ, Med Imaging Ctr, Affiliated Hosp, Weifang 261053, Shandong, Peoples R China 7.Weifang Second Peoples Hosp, 7 Yuanxiao St, Weifang 261053, Shandong, Peoples R China 8.Weifang Med Univ, Clin Competency Training Ctr, Med Expt & Training Ctr, Weifang 261053, Shandong, Peoples R China 9.Qingdao Univ, Dept Hepatobiliary & Pancreat Surg, Affiliated Hosp, Qingdao 266003, Peoples R China 10.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing 100101, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Zixun,Hu, Xinyu,Wang, Zhongyi,et al. Ketamine alleviates PTSD-like effect and improves hippocampal synaptic plasticity via regulation of GSK-3(3/GR (3 /GR signaling of rats[J]. JOURNAL OF PSYCHIATRIC RESEARCH,2024,178:259-269. |
| APA | Wang, Zixun.,Hu, Xinyu.,Wang, Zhongyi.,Chen, Jiaming.,Wang, Ling.,...&Sun, Lin.(2024).Ketamine alleviates PTSD-like effect and improves hippocampal synaptic plasticity via regulation of GSK-3(3/GR (3 /GR signaling of rats.JOURNAL OF PSYCHIATRIC RESEARCH,178,259-269. |
| MLA | Wang, Zixun,et al."Ketamine alleviates PTSD-like effect and improves hippocampal synaptic plasticity via regulation of GSK-3(3/GR (3 /GR signaling of rats".JOURNAL OF PSYCHIATRIC RESEARCH 178(2024):259-269. |
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来源：心理研究所
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