PMID- 30316917 OWN - NLM STAT- MEDLINE DCOM- 20190930 LR - 20211204 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 143 DP - 2018 Oct TI - Essential roles of neuropeptide VGF regulated TrkB/mTOR/BICC1 signaling and phosphorylation of AMPA receptor subunit GluA1 in the rapid antidepressant-like actions of ketamine in mice. PG - 58-65 LID - S0361-9230(18)30583-5 [pii] LID - 10.1016/j.brainresbull.2018.10.004 [doi] AB - 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 GluA1 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 GluA1 phosphorylation. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Shen, Mengxin AU - Shen M AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. FAU - Lv, Dan AU - Lv D AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. FAU - Liu, Xu AU - Liu X AD - Department of Pharmacy, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, PR China. FAU - Li, Shuting AU - Li S AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. FAU - Chen, Yaping AU - Chen Y AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. FAU - Zhang, Yanhua AU - Zhang Y AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. FAU - Wang, Zhen AU - Wang Z AD - CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: wangzhen@simm.ac.cn. FAU - Wang, Chuang AU - Wang C AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. Electronic address: wanglovechuang@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181011 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Antidepressive Agents) RN - 0 (Bicc1 protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (Neuropeptides) RN - 0 (RNA-Binding Proteins) RN - 0 (Receptors, AMPA) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (VGF peptide) RN - 690G0D6V8H (Ketamine) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.28 (tropomyosin kinase) SB - IM MH - Animals MH - Antidepressive Agents/pharmacology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Depression/metabolism MH - Gene Knockdown Techniques MH - Hippocampus/drug effects MH - Ketamine/pharmacology MH - Male MH - Membrane Glycoproteins/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neuropeptides/*metabolism MH - Phosphorylation/drug effects MH - Prefrontal Cortex/drug effects MH - Protein Kinases/metabolism MH - Protein-Tyrosine Kinases/*metabolism MH - RNA-Binding Proteins/*metabolism MH - Receptor, trkB/metabolism MH - Receptors, AMPA/drug effects/metabolism MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism MH - Signal Transduction/drug effects MH - Stress, Psychological/metabolism MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - BICC1 OT - Ketamine OT - TrkB OT - VGF OT - mTOR EDAT- 2018/10/15 06:00 MHDA- 2019/10/01 06:00 CRDT- 2018/10/15 06:00 PHST- 2018/07/31 00:00 [received] PHST- 2018/09/27 00:00 [revised] PHST- 2018/10/09 00:00 [accepted] PHST- 2018/10/15 06:00 [pubmed] PHST- 2019/10/01 06:00 [medline] PHST- 2018/10/15 06:00 [entrez] AID - S0361-9230(18)30583-5 [pii] AID - 10.1016/j.brainresbull.2018.10.004 [doi] PST - ppublish SO - Brain Res Bull. 2018 Oct;143:58-65. doi: 10.1016/j.brainresbull.2018.10.004. Epub 2018 Oct 11.