Sevoflurane acts as an antidepressant by suppression of GluN2D-containing NMDA receptors on interneurons
文献类型：期刊论文
| 作者 | Guo, Fei6,7; Zhang, Bing7; Shen, Fuyi7; Li, Qian7; Song, Yingcai7; Li, Tianyu7; Zhang, Yongmei5; Du, Weijia7; Li, Yuanxi4; Liu, Wei7 |
| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
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| 出版日期 | 2024-05-23 |
| 页码 | 20 |
| 关键词 | antidepressant disinhibition GluN2D subunits interneurons sevoflurane |
| ISSN号 | 0007-1188 |
| DOI | 10.1111/bph.16420 |
| 通讯作者 | Zhang, Bing(bingozzz@126.com) ; Li, Yang(liyang@simm.ac.cn) ; Liu, Zhiqiang(drliuzhiqiang@163.com) |
| 英文摘要 | Background and PurposeSevoflurane, a commonly used inhaled anaesthetic known for its favourable safety profile and rapid onset and offset, has not been thoroughly investigated as a potential treatment for depression. In this study, we reveal the mechanism through which sevoflurane delivers enduring antidepressant effects.Experimental ApproachTo assess the antidepressant effects of sevoflurane, behavioural tests were conducted, along with in vitro and ex vivo whole-cell patch-clamp recordings, to examine the effects on GluN1-GluN2 incorporated N-methyl-d-aspartate (NMDA) receptors (NMDARs) and neuronal circuitry in the medial prefrontal cortex (mPFC). Multiple-channel electrophysiology in freely moving mice was performed to evaluate sevoflurane's effects on neuronal activity, and GluN2D knockout (grin2d-/-) mice were used to confirm the requirement of GluN2D for the antidepressant effects.Key ResultsRepeated exposure to subanaesthetic doses of sevoflurane produced sustained antidepressant effects lasting up to 2 weeks. Sevoflurane preferentially inhibited GluN2C- and GluN2D-containing NMDARs, causing a reduction in interneuron activity. In contrast, sevoflurane increased action potentials (AP) firing and decreased spontaneous inhibitory postsynaptic current (sIPSC) in mPFC pyramidal neurons, demonstrating a disinhibitory effect. These effects were absent in grin2d-/- mice, and both pharmacological blockade and genetic knockout of GluN2D abolished sevoflurane's antidepressant actions, suggesting that GluN2D is essential for its antidepressant effect.Conclusion and ImplicationsSevoflurane directly targets GluN2D, leading to a specific decrease in interneuron activity and subsequent disinhibition of pyramidal neurons, which may underpin its antidepressant effects. Targeting the GluN2D subunit could hold promise as a potential therapeutic strategy for treating depression. image |
| WOS关键词 | STAR-ASTERISK-D ; VOLATILE ANESTHETICS ; CONCISE GUIDE ; DEPRESSION ; CORTEX ; MECHANISMS ; KETAMINE ; SUBUNIT ; EXPRESSION ; SYNAPSES |
| 资助项目 | National Natural Science Foundation of China ; National Major Scientific and Technological Special Project for 'Significant New Drugs Development'[2019zx09301102] ; Natural Science Foundation of Shanghai[22ZR1449300] ; Program of Shanghai Academic Research Leader[22XD1402400] ; Shanghai Science and Technology Commission[23S11900600] ; Clinical Research Project of Shanghai Municipal Health Commission[202140253] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040220] ; [82371533] ; [31671049] ; [82271582] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001229290100001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311105]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Bing; Li, Yang; Liu, Zhiqiang |
| 作者单位 | 1.Tongji Univ, Sch Med, Anesthesia & Brain Funct Res Inst, Shanghai, Peoples R China 2.Chinese Acad Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Neurosci, Shanghai, Peoples R China 3.Anhui Univ Chinese Med, Sch Pharm, Hefei, Peoples R China 4.East China Univ Sci & Technol, Inst Cognit Neurodynam, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Tongji Univ, Shanghai Matern & Infant Hosp 1, Clin & Translat Res Ctr,Shanghai Key Lab Maternal, Sch Med,Shanghai Inst Maternal Fetal Med & Gynecol, Shanghai 201204, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Fei,Zhang, Bing,Shen, Fuyi,et al. Sevoflurane acts as an antidepressant by suppression of GluN2D-containing NMDA receptors on interneurons[J]. BRITISH JOURNAL OF PHARMACOLOGY,2024:20. |
| APA | Guo, Fei.,Zhang, Bing.,Shen, Fuyi.,Li, Qian.,Song, Yingcai.,...&Liu, Zhiqiang.(2024).Sevoflurane acts as an antidepressant by suppression of GluN2D-containing NMDA receptors on interneurons.BRITISH JOURNAL OF PHARMACOLOGY,20. |
| MLA | Guo, Fei,et al."Sevoflurane acts as an antidepressant by suppression of GluN2D-containing NMDA receptors on interneurons".BRITISH JOURNAL OF PHARMACOLOGY (2024):20. |
入库方式： OAI收割
来源：上海药物研究所
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