Positive Allosteric Modulation of AMPAR by PF-4778574 Produced Rapid Onset Antidepressant Actions in Mice
文献类型：期刊论文
| 作者 | Shen, Mengxin1; Lv, Dan1; Li, Shuting1; Zhang, Yanhua1; Wang, Zhen2 ; Zhao, Chiyu1; Chen, Xuejie1; Wang, Chuang1
|
| 刊名 | Cerebral cortex (New York, N.Y. : 1991)
 |
| 出版日期 | 2018-12-19 |
| ISSN号 | 1460-2199 |
| DOI | 10.1093/cercor/bhy324 |
| 文献子类 | Article |
| 英文摘要 | It has been reported that fast-acting antidepressants enhance glutamatergic neurotransmission in the prefrontal cortex (PFC) regions via alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation. However, the precise mechanisms underlying the fast-acting antidepressants lead to an activation of AMPAR pathways remain largely unclear. To address this issue, a novel AMPAR positive allosteric agonist, PF-4778574, was used to test the rapid effects and the role of VGF (nonacronymic)/brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/AKT signaling in these actions in mice. We found that PF-4778574 rapidly alleviated chronic unpredictable stress-induced depression-like behaviors in a concentration-dependent manner. In addition, knock down of vesicular glutamate transporter 1 (VGLUT1) in the PFC of mice induced depression-like behaviors, whereas treatment with PF-4778574 was sufficient to alleviate it, indicating a presynaptic VGLUT1 independent effect. Furthermore, we demonstrate that pharmacological inhibitors of AMPAR or of L-type voltage-dependent Ca2+ channel (L-VDCC) blocked the antidepressants' effect on behaviors and the upregulation on the AMPAR-mediated VGF/BDNF/TrkB/AKT signaling of PF-4778574. Together, our findings indicate that postsynaptic AMPAR activation followed by activation of L-VDCC and subsequent VGF/BDNF/TrkB/AKT signaling are required for the rapid antidepressant effects of PF-4778574. Our data support a promising therapeutic profile for PF-4778574 as a new fast-acting antidepressant. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266803]  |
| 专题 | 药物化学研究室 |
| 作者单位 | 1.Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, China; 2.CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China |
| 推荐引用方式 GB/T 7714 | Shen, Mengxin,Lv, Dan,Li, Shuting,et al. Positive Allosteric Modulation of AMPAR by PF-4778574 Produced Rapid Onset Antidepressant Actions in Mice[J]. Cerebral cortex (New York, N.Y. : 1991),2018. |
| APA | Shen, Mengxin.,Lv, Dan.,Li, Shuting.,Zhang, Yanhua.,Wang, Zhen.,...&Wang, Chuang.(2018).Positive Allosteric Modulation of AMPAR by PF-4778574 Produced Rapid Onset Antidepressant Actions in Mice.Cerebral cortex (New York, N.Y. : 1991). |
| MLA | Shen, Mengxin,et al."Positive Allosteric Modulation of AMPAR by PF-4778574 Produced Rapid Onset Antidepressant Actions in Mice".Cerebral cortex (New York, N.Y. : 1991) (2018). |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。