(2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models
文献类型：期刊论文
| 作者 | Li, Yu8; Du, YaLin5; Wang, Chen8; Lu, GuoHua8; Sun, HongWei8; Kong, YuJia4; Wang, WeiWen3 ; Lian, Bo2; Li, ChangJiang8; Wang, Ling1
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| 刊名 | NEUROBIOLOGY OF STRESS
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| 出版日期 | 2022-11-01 |
| 卷号 | 21页码:14 |
| ISSN号 | 2352-2895 |
| 关键词 | Post-traumatic stress disorder (PTSD) (2R,6R)-Hydroxynorketamine ((2R,6R)-HNK) Synaptic plasticity Glutamatergic nervous system GluA1 |
| DOI | 10.1016/j.ynstr.2022.100503 |
| 通讯作者 | Zhang, XianQiang(xianqiang2018@163.com) ; Sun, Lin(linsun2013@wfmc.edu.cn) |
| 英文摘要 | Post-traumatic stress disorder (PTSD) is a debilitating mental disorder with high morbidity and great social and economic relevance. However, extant pharmacotherapies of PTSD require long-term use to maintain effectiveness and have enormous side effects. The glutamatergic system, especially the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), is an important target of current research on the mechanism of PTSD. Postsynaptic AMPAR function and expression are known to be increased by (2R, 6R)-hydronorketamine (HNK), the primary metabolite of ketamine. However, whether (2R,6R)-HNK alleviates PTSD-like effects via AMPAR upregulation is yet to be known. In the present study, rats were exposed to single prolonged stress and electric foot shock (SPS&S). Afterwards, gradient concentrations of (2R,6R)-HNK (20, 50, and 100 mu M) were administered by intracerebroventricular (i.c.v.) injection. Open field, elevated plus maze, freezing behavior, and forced swimming tests were used to examine PTSD-like symptoms. In addition, the protein levels of GluA1, BDNF and PSD-95 were analyzed using western blotting and immunofluorescence, and the synaptic ultrastructure of the prefrontal cortex (PFC) was observed by transmission electron microscopy. We found that (2R,6R)-HNK changed SPS&S-induced behavioral expression, such as increasing autonomous activity and residence time in the open arm and decreasing immobility time. Likewise, (2R,6R)-HNK (50 mu M) increased GluA1, BDNF, and PSD-95 protein expression in the PFC. Changes in synaptic ultrastructure induced by SPS&S were reversed by administration of (2R,6R)-HNK. Overall, we find that (2R,6R)-HNK can ameliorate SPS&S-induced fear avoidance in rats, as well as rat cognates of anxiety and depression. This may be related to GluA1-mediated synaptic plasticity in the PFC. |
| 收录类别 | SCI |
| WOS关键词 | POSTTRAUMATIC-STRESS-DISORDER ; INDEPENDENT ANTIDEPRESSANT ACTIONS ; TRAUMATIC BRAIN-INJURY ; KETAMINE METABOLITE ; EFFICACY ; BDNF ; HIPPOCAMPUS ; DYSFUNCTION ; EXTINCTION ; BEHAVIOR |
| 资助项目 | National Natural Science Foundation of China[82101588] ; National Natural Science Foundation of China[82071517] ; National Natural Science Foundation of China[31771217] ; Ministry of Science and Technology of China[2017YFE0126500] ; Natural Science Foundation of Shandong Province[ZR2020MC218] ; Institute of Psychology, Chinese Academy of Sciences[GJ202002] ; Medical Education Research project of Chinese Medical Association[20A1209] ; Education teaching reform and research found of Weifang Medical University[2019YB023] ; Science and Technology Development Program of Traditional Chinese Medicine in Shandong Province[2019WS594/202002010572] ; Education and Teaching Reform Project of the Psychology and Education Reference Committee of the Ministry of Education, Curriculum Construction Class-13[20221013] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCIENCE INC |
| WOS记录号 | WOS:000892932100001 |
| 资助机构 | National Natural Science Foundation of China ; Ministry of Science and Technology of China ; Natural Science Foundation of Shandong Province ; Institute of Psychology, Chinese Academy of Sciences ; Medical Education Research project of Chinese Medical Association ; Education teaching reform and research found of Weifang Medical University ; Science and Technology Development Program of Traditional Chinese Medicine in Shandong Province ; Education and Teaching Reform Project of the Psychology and Education Reference Committee of the Ministry of Education, Curriculum Construction Class-13 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/44120]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 通讯作者 | Zhang, XianQiang; Sun, Lin |
| 作者单位 | 1.Weifang Med Univ, Clin Competency Training Ctr, Med Expt & Training Ctr, Weifang, Peoples R China 2.Weifang Med Univ, Dept Biosci & Technol, 7166 Baotong West St, Weifang 261053, Shandong, Peoples R China 3.Chinese Acad Sci, Inst Psychol, Beijing, Peoples R China 4.Weifang Med Univ, Sch Publ Hlth, 7166 Baotong West St, Weifang 261053, Shandong, Peoples R China 5.Weifang Med Univ, Sch Clin Med, 7166 Baotong West St, Weifang 261053, Shandong, Peoples R China 6.Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China 7.Peking Univ, Minist Hlth, Hosp 6, Inst Mental Hlth, Beijing, Peoples R China 8.Weifang Med Univ, Sch Psychol, 7166 Baotong West St, Weifang 261053, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yu,Du, YaLin,Wang, Chen,et al. (2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models[J]. NEUROBIOLOGY OF STRESS,2022,21:14. |
| APA | Li, Yu.,Du, YaLin.,Wang, Chen.,Lu, GuoHua.,Sun, HongWei.,...&Sun, Lin.(2022).(2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models.NEUROBIOLOGY OF STRESS,21,14. |
| MLA | Li, Yu,et al."(2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models".NEUROBIOLOGY OF STRESS 21(2022):14. |
入库方式： OAI收割
来源：心理研究所
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