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The rapid antidepressant and anxiolytic-like effects of YY-21 involve enhancement of excitatory synaptic transmission via activation of mTOR signaling in the mPFC

文献类型：期刊论文

作者Guo, Fei1; Zhang, Bing1,2; Fu, Zhiwen1,2; Ma, Yuqin1,2; Gao, Yu1,2; Shen, Fuyi1,2; Huang, Chenggang1; Li, Yang1
刊名EUROPEAN NEUROPSYCHOPHARMACOLOGY
出版日期2016-07
卷号26期号:7页码:1087-1098
关键词YY-21 mTOR Synaptic transmission Synaptic proteins
ISSN号0924-977X
DOI10.1016/j.euroneuro.2016.05.006
文献子类Article
英文摘要Although antidepressants have been widely prescribed to treat patients with major depressive disease (MDD), there is little disagreement over the need for improved antidepressant therapeutics as the typical treatments have a slow therapeutic onset and moderate efficacy. In the present study, we assessed a novel compound, YY-21, from timosaponin B-III derived from sarsasapogenin of Anemarrhenae Rhizoma. From the initial results, we found that YY-21 obviously increased presynaptic glutamate release and enhanced long-term synaptic activity within 10 min as determined by excitatory postsynaptic current (EPSC) and field excitatory postsynaptic potential (fEPSP) in medial prefrontal cortex (mPFC) slices, respectively. YY-21 demonstrated anxiolytic-like effects following acute administration in naive animals and reversed the depressive-like and anxiety phenotypes induced by chronic unpredictable mild stress (CMS) with a relatively fast therapeutic onset. Furthermore, analysis of intracellular signaling pathways showed that YY-21 normalized the CMS-induced low protein levels of GluN2B, p-mTOR, synaptic-related proteins, such as BDNF, PSD-95 and GluA1. Pre-application of the mTOR-selective inhibitor rapamycin blocked YY-21-induced long-term synaptic enhancement. These findings suggest that the activation of BDNF-dependent mTOR signaling, which produces a rapid increase in the postsynaptic protein PSD-95 and GluA1 and further triggers the long-term enhancement of synaptic neurotransmission, may be the mechanism underlying the rapid antidepressant and anxiolytic effects induced by YY-21. (C) 2016 Elsevier B.V. and ECNP. All rights reserved.
WOS关键词UNIPOLAR MOOD DISORDERS ; STAR-ASTERISK-D ; ANXIETY DISORDERS ; DEPRESSION ; STRESS ; BDNF ; CORTEX ; COMORBIDITY ; ANTAGONISTS ; MECHANISMS
资助项目National Natural Science Foundation[31200771] ; National Natural Science Foundation[81030065] ; National Natural Science Foundation[81274055] ; National Natural Science Foundation[3137106601] ; National Natural Science Foundation[3117101101] ; Ministry of Science and Technology[2013CB91060101] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2012ZX09301-001-06] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2014ZX09102001-005]
WOS研究方向Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
语种英语
WOS记录号WOS:000383340100001
出版者ELSEVIER SCIENCE BV
源URL[http://119.78.100.183/handle/2S10ELR8/275965]  
专题药理学第二研究室
上海中药现代化研究中心
通讯作者Guo, Fei; Huang, Chenggang; Li, Yang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China;
2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Guo, Fei,Zhang, Bing,Fu, Zhiwen,et al. The rapid antidepressant and anxiolytic-like effects of YY-21 involve enhancement of excitatory synaptic transmission via activation of mTOR signaling in the mPFC[J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY,2016,26(7):1087-1098.
APA Guo, Fei.,Zhang, Bing.,Fu, Zhiwen.,Ma, Yuqin.,Gao, Yu.,...&Li, Yang.(2016).The rapid antidepressant and anxiolytic-like effects of YY-21 involve enhancement of excitatory synaptic transmission via activation of mTOR signaling in the mPFC.EUROPEAN NEUROPSYCHOPHARMACOLOGY,26(7),1087-1098.
MLA Guo, Fei,et al."The rapid antidepressant and anxiolytic-like effects of YY-21 involve enhancement of excitatory synaptic transmission via activation of mTOR signaling in the mPFC".EUROPEAN NEUROPSYCHOPHARMACOLOGY 26.7(2016):1087-1098.

入库方式： OAI收割

来源：上海药物研究所

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