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

doi:10.1016/j.euroneuro.2016.05.006

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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
	Guo, Fei 1; Zhang, Bing 1,2; Fu, Zhiwen 1,2; Ma, Yuqin 1,2; Gao, Yu 1,2; Shen, Fuyi 1,2; Huang, Chenggang1 ; Li, Yang1
刊名	EUROPEAN NEUROPSYCHOPHARMACOLOGY
	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
DOI	10.1016/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.
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关键词	UNIPOLAR MOOD DISORDERS ; STAR-ASTERISK-D ; ANXIETY DISORDERS ; DEPRESSION ; STRESS ; BDNF ; CORTEX ; COMORBIDITY ; ANTAGONISTS ; MECHANISMS
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000383340100001
内容类型	期刊论文
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.