A novel positive modulator of GABAA receptor exhibiting antidepressive properties
文献类型：期刊论文
| 作者 | Zheng, Yin-Li1; Shen, Fu-Yi2; Wang, Yang3; Pan, Jing-Pei4; Wang, Xian5; Li, Tian-Yu2,4,6; Du, Wei-Jia2; Liu, Zhi-Qiang2,4,6; Li, Yang1,4 ; Guo, Fei1,4
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| 刊名 | Sheng li xue bao : [Acta physiologica Sinica]
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| 出版日期 | 2024-10-25 |
| 卷号 | 76期号:5页码:677-690 |
| 关键词 | antidepressant GABAA receptor positive modulator neurotransmission |
| 文献子类 | Article |
| 英文摘要 | gamma-Aminobutyric acid (GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABAA receptor positive allosteric modulators are emerging as promising in clinical practice, their precise antidepressant mechanism remains to be further elucidated. The aim of the present study was to investigate the effects of LY-02, a novel compound derived from the metabolite of timosaponin, on depression in animals and its mechanism. The results of behavioral tests showed that LY-02 exhibited better antidepressant effects in both male C57BL/6 mice and Sprague Dawley (SD) rats. The results of cellular voltage clamp experiments showed that LY-02 enhanced GABA-mediated currents in HEK293T cells expressing recombinant alpha6beta3delta subunit-containing GABAA receptors. Electrophysiological recording from brain slices showed that LY-02 decreased the amplitude of spontaneous inhibitory postsynaptic current (sIPSC) and increased action potentials of pyramidal neurons in the medial prefrontal cortex (mPFC) of C57BL/6 mice. Western blot results showed that LY-02 dose-dependently up-regulated the protein expression levels of brain-derived neurotrophic factor (BDNF), tropomyosin related kinase B (TrkB) and postsynaptic density protein 95 (PSD-95) in mPFC of mice. The above results suggest that LY-02, as a positive modulator of GABAA receptors, reduces inhibitory neurotransmission in pyramidal neurons. It further activates the BDNF/TrkB signaling pathway, thus exerting antidepressant effects. It suggests that LY-02 is a potential novel therapeutic agent for depression treatment. |
| 语种 | 英语 |
| WOS记录号 | MEDLINE:39468805 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317009]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Yang; Guo, Fei |
| 作者单位 | 1.School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China 2.Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China 3.Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China 4.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China 5.School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China 6.Anesthesia and Brain Function Research Institute, Tongji University School of Medicine, Shanghai 200082, China |
| 推荐引用方式 GB/T 7714 | Zheng, Yin-Li,Shen, Fu-Yi,Wang, Yang,et al. A novel positive modulator of GABAA receptor exhibiting antidepressive properties[J]. Sheng li xue bao : [Acta physiologica Sinica],2024,76(5):677-690. |
| APA | Zheng, Yin-Li.,Shen, Fu-Yi.,Wang, Yang.,Pan, Jing-Pei.,Wang, Xian.,...&Guo, Fei.(2024).A novel positive modulator of GABAA receptor exhibiting antidepressive properties.Sheng li xue bao : [Acta physiologica Sinica],76(5),677-690. |
| MLA | Zheng, Yin-Li,et al."A novel positive modulator of GABAA receptor exhibiting antidepressive properties".Sheng li xue bao : [Acta physiologica Sinica] 76.5(2024):677-690. |
入库方式： OAI收割
来源：上海药物研究所
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