Essential roles of neuropeptide VGF regulated TrkB/mTOR/BICC1 signaling and phosphorylation of AMPA receptor subunit GluAl in the rapid antidepressant-like actions of ketamine in mice
Shen, Mengxin2,3,4; Lv, Dan2,3,4; Liu, Xu1; Li, Shuting2,3,4; Chen, Yaping2,3,4; Zhang, Yanhua2,3,4; Wang, Zhen5; Wang, Chuang2,3,4
刊名BRAIN RESEARCH BULLETIN
2018-10
卷号143页码:58-65
关键词VGF Ketamine TrkB mTOR BICC1
ISSN号0361-9230
DOI10.1016/j.brainresbull.2018.10.004
文献子类Article
英文摘要Previous studies have suggested that rapid reductions in depression-like behaviors are observed in response to sub-anesthetic-doses of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist. Neuropeptide VGF (non-acronymic) is a critical effector of depression-like behaviors and is thought to be involved in the antidepressant actions of ketamine that have been demonstrated. However, the mechanism underlying the involvement of VGF in the anti-depressant action of ketamine remains unclear. We found that single dose ketamine treatment reversed CSDS-induced depression-like behaviors and decrease of VGF in the PFC of mice. To investigate the involvement of VGF in the antidepressant-like effects of ketamine, a lentivirus vector for VGF was constructed to knockdown the expression of VGF in the prefrontal cortex (PFC) of mice. The biochemical and behavioral effects of this VGF knockdown were examined, using the open field, forced swim, and sucrose preference tests. Our results show that knockdown of VGF increased the immobility time and decreased the sucrose preference in mice. These effects were not improved by ketamine administration. In addition, we found that knockdown of VGF significantly decreased the expression of phosphorylation of tropomyosin receptor kinase B (TrkB), mammalian target of rapamycin (mTOR), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluAl Ser845 and increased the expression of bicaudal C homolog 1 (BICC1) in the mouse PFC, and blocked the regulation of TrkB/mTOR/BICC1 signaling and GluA1 phosphorylation by ketamine. Our results indicate that the rapid onset antidepressant-like actions of ketamine require VGF to regulate TrkB/mTOR/BICC1 signaling and AMPA receptor GluAl phosphorylation.
资助项目National Natural Science Foundation of China[81671337] ; National Natural Science Foundation of China[81201050] ; Natural Science Foundation of Zhejiang province[LQ12H09001] ; Natural Science Foundation of Ningbo[2017A610212] ; Ningbo Municipal Innovation Team of Life Science and Health[2015C110026] ; National Undergraduate Training Program for Innovation and Entrepreneurship[201711646017] ; Student Research and Innovation Program[00000000] ; K.C. Wong Magna - Ningbo University[00000000]
WOS关键词DEPRESSION ; INHIBITION ; BEHAVIOR ; BICC1 ; ASSOCIATION ; CONTRIBUTES ; EXPRESSION
WOS研究方向Neurosciences & Neurology
语种英语
出版者PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号WOS:000452813700007
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/279543]  
专题药物化学研究室
通讯作者Wang, Zhen; Wang, Chuang
作者单位1.Gen Hosp Chinese Peoples Armed Police Forces, Dept Pharm, Beijing 100039, Peoples R China;
2.Ningbo Univ, Sch Med, Ningbo Key Lab Behav Neurosci, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China;
3.Ningbo Univ, Sch Med, Zhejiang Prov Key Lab Pathophysiol, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China;
4.Ningbo Univ, Sch Med, Dept Physiol & Pharmacol, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
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Shen, Mengxin,Lv, Dan,Liu, Xu,et al. Essential roles of neuropeptide VGF regulated TrkB/mTOR/BICC1 signaling and phosphorylation of AMPA receptor subunit GluAl in the rapid antidepressant-like actions of ketamine in mice[J]. BRAIN RESEARCH BULLETIN,2018,143:58-65.
APA Shen, Mengxin.,Lv, Dan.,Liu, Xu.,Li, Shuting.,Chen, Yaping.,...&Wang, Chuang.(2018).Essential roles of neuropeptide VGF regulated TrkB/mTOR/BICC1 signaling and phosphorylation of AMPA receptor subunit GluAl in the rapid antidepressant-like actions of ketamine in mice.BRAIN RESEARCH BULLETIN,143,58-65.
MLA Shen, Mengxin,et al."Essential roles of neuropeptide VGF regulated TrkB/mTOR/BICC1 signaling and phosphorylation of AMPA receptor subunit GluAl in the rapid antidepressant-like actions of ketamine in mice".BRAIN RESEARCH BULLETIN 143(2018):58-65.
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