TREK1 channel blockade induces an antidepressant-like response synergizing with 5-HT1A receptor signaling
文献类型：期刊论文
| 作者 | Ye, Dongqing3; Li, Yang1 ; Zhang, Xiangrong2; Guo, Fei1; Geng, Leiyu3; Zhang, Qi1; Zhang, Zhijun3
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| 刊名 | EUROPEAN NEUROPSYCHOPHARMACOLOGY
 |
| 出版日期 | 2015-12 |
| 卷号 | 25期号:12页码:2426-2436 |
| 关键词 | TWIK-related mechano-gated K+ channel (TREK1) Antidepressant SID1900 5-HT1A receptor Chronic unpredictable mild stress (CUMS) Brain derived neurotrophic factor (BDNF) |
| ISSN号 | 0924-977X |
| DOI | 10.1016/j.euroneuro.2015.09.007 |
| 文献子类 | Article |
| 英文摘要 | Current antidepressants often remain the inadequate efficacy for many depressive patients, which warrant the necessary endeavor to develop the new molecules and targets for treating depression. Recently, the two-pore domain potassium channel TREK1 has been implicated in mood regulation and TREK-1 antagonists could be the promising antidepressant. This study has screened a TREK1 blocker (SID1900) with a satisfactory blood-brain barrier permeation and bioavailability. Electrophysiological research has shown that SID1900 and the previously reported TREK1 blocker (spadin) efficiently blocked TREK-1 current in HEK293 cells and specifically blocked two-pore domain potassium channels in primary-cultured rat hippocampal neurons. SID1900 and spadin induced a significant antidepressant-like response in the rat model of chronic unpredictable mild stress (CUMS). Both two TREK1 blockers substantially increased the firing rate of 5-HT-ergic neurons in the dorsal raphe nuclei (DRN) and PFC of CUMS rats. SID1900 and spadin significantly up-regulated the expression of PKA-pCREB-BDNF signaling in DRN, hippocampus and PFC of CUMS rats, which were enhanced and reversed by a 5-HTR1A agonist (8-OH-DPAT) and antagonist (WAY100635) respectively. The present findings suggested that TREK1 channel blockers posses the substantial antidepressant-like effect and have the potential synergistic effect with 5-HT1A receptor activation through the common CREB-BDNF signal transduction. (C) 2015 Elsevier B.V. and ECNR All rights reserved. |
| WOS关键词 | CHRONIC MILD STRESS ; MAJOR DEPRESSIVE DISORDER ; MEDIAL PREFRONTAL CORTEX ; POTASSIUM CHANNEL ; RAT ; TRANSMISSION ; MECHANISMS ; EXPRESSION ; NEURONS |
| 资助项目 | National Natural Science Foundation of China[30770779] ; National Natural Science Foundation of China[31371074] ; China-Canada Joint Health Research Initiative[81061120529] ; National Key Science Technology Program in the 12th Five Year Plan of China (The Project of New Drug Formulation)[2012ZX09506-001-009] ; Key Program for Clinical Medicine and Science and Technology: Jiangsu Provence Clinical Medical Research Center[BL2013025] |
| WOS研究方向 | Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry |
| 语种 | 英语 |
| WOS记录号 | WOS:000366947300025 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276301]  |
| 专题 | 药理学第二研究室 药物质量控制与固体化学研究中心 药物安全性评价中心 |
| 通讯作者 | Zhang, Zhijun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Pharmacol Lab, Shanghai 201203, Peoples R China; 2.Nanjing Med Univ, Nanjing Brain Hosp, Neurol Dept, Nanjing 210029, Jiangsu, Peoples R China 3.Southeast Univ, Neuropsychiatr Inst, Sch Med, Neurol Dept,Affiliated ZhongDa Hosp, Nanjing 210009, Jiangsu, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Ye, Dongqing,Li, Yang,Zhang, Xiangrong,et al. TREK1 channel blockade induces an antidepressant-like response synergizing with 5-HT1A receptor signaling[J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY,2015,25(12):2426-2436. |
| APA | Ye, Dongqing.,Li, Yang.,Zhang, Xiangrong.,Guo, Fei.,Geng, Leiyu.,...&Zhang, Zhijun.(2015).TREK1 channel blockade induces an antidepressant-like response synergizing with 5-HT1A receptor signaling.EUROPEAN NEUROPSYCHOPHARMACOLOGY,25(12),2426-2436. |
| MLA | Ye, Dongqing,et al."TREK1 channel blockade induces an antidepressant-like response synergizing with 5-HT1A receptor signaling".EUROPEAN NEUROPSYCHOPHARMACOLOGY 25.12(2015):2426-2436. |
入库方式： OAI收割
来源：上海药物研究所
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