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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, Fei1; Zhang, Bing1,2; Fu, Zhiwen1,2; Ma, Yuqin1,2; Gao, Yu1,2; Shen, Fuyi1,2; Huang, Chenggang1; Li, Yang1
刊名European neuropsychopharmacology
2016-07-01
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
通讯作者Guo, fei(guofei@simm.ac.cn) ; Huang, chenggang(cghuang@simm.ac.cn) ; Li, yang(liyang@simm.ac.cn)
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
WOS研究方向Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
WOS类目Clinical Neurology ; Neurosciences ; 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
URI标识http://www.corc.org.cn/handle/1471x/2376079
专题中国科学院大学
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
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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.
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