PMID- 24631486 OWN - NLM STAT- MEDLINE DCOM- 20141209 LR - 20220309 IS - 1873-5177 (Electronic) IS - 0091-3057 (Linking) VI - 120 DP - 2014 May TI - The VGF-derived peptide TLQP62 produces antidepressant-like effects in mice via the BDNF/TrkB/CREB signaling pathway. PG - 140-8 LID - S0091-3057(14)00073-2 [pii] LID - 10.1016/j.pbb.2014.03.003 [doi] AB - Recent studies demonstrate that the neuropeptide VGF (nonacronymic)-derived peptide is regulated in the hippocampus by antidepressant therapies. Brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), cAMP response element-binding protein (CREB) signaling, and monoamine transmitter pathways mediate the behavioral effects of antidepressants, but it is not known if these pathways also contribute to the antidepressant-like effects of VGF-derived peptide TLQP62. Here the antidepressant-like effects of TLQP62 were evaluated by measuring immobility time in the forced swimming and tail suspension tests (FST and TST) following acute microinjection of the TLQP62 (0.25, 0.5 and 1 nmol/side) into the hippocampal CA1 regions. This treatment dose-dependently reduced immobility in the FST and TST compared to phosphate-buffered saline (PBS) infusion without affecting locomotor activity in the open field test (OFT). In addition, daily intrahippocampal microinfusion of TLQP62 (1 nmol/side/day; 21 days) also upregulated the expression of BDNF and the phosphorylation of CREB (pCREB) and TrkB (pTrkB) without altering CREB or TrkB. Blocking tissue plasminogen activator (tPA) by microinfusion of tPASTOP or TrkB activation by microinfusion of K252a 60 min prior to TLQP62 infusion almost completely abolished TLQP62-induced antidepressant-like effects, BDNF upregulation, and CREB/TrkB phosphorylation. In contrast, none of these effects were diminished by pretreatment with the non-specific 5-HT receptor antagonist metergoline, the selective 5-HT1A receptor antagonist NAN-190, the 5-HT synthase inhibitor parachlorophenylalanine, the selective alpha1-adrenoceptor antagonist prazosin, the beta receptor antagonist propranolol, or the D2 receptor antagonist raclopride. Moreover, our study was also to investigate the antidepressant-like effects of TLQP62 (50, 250 and 500 nmol/kg; i.p.) on depression-related behaviors in comparison with fluoxetine (10mg/kg; i.p.). While TLQP62 and fluoxetine showed similar antidepressant-like behavioral effects in the FST of mice. Our present results strongly suggest that activation of BDNF/TrkB/CREB signaling may be involved in the antidepressant-like effects of TLQP62. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Lin, Peipei AU - Lin P AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Wang, Chuang AU - Wang C AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. Electronic address: wangchuang@nbu.edu.cn. FAU - Xu, Bing AU - Xu B AD - No. 97 Hospital, Xuzhou, Jiangsu 221000, PR China. FAU - Gao, Siyun AU - Gao S AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Guo, Jiejie AU - Guo J AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Zhao, Xin AU - Zhao X AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Huang, Huihui AU - Huang H AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Zhang, Junfang AU - Zhang J AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Chen, Xiaowei AU - Chen X AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Wang, Qinwen AU - Wang Q AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. FAU - Zhou, Wenhua AU - Zhou W AD - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology of Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140311 PL - United States TA - Pharmacol Biochem Behav JT - Pharmacology, biochemistry, and behavior JID - 0367050 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Neuropeptides) RN - 0 (Peptides) RN - 0 (TLQP62 peptide) RN - 0 (VGF peptide) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Antidepressive Agents/*pharmacology MH - Brain-Derived Neurotrophic Factor/*antagonists & inhibitors MH - Cyclic AMP Response Element-Binding Protein/*antagonists & inhibitors MH - Depressive Disorder/drug therapy/psychology MH - Hindlimb Suspension MH - Male MH - Mice MH - Mice, Inbred ICR MH - Motor Activity/drug effects MH - Neuropeptides/*pharmacology MH - Peptides/*pharmacology MH - Receptor, trkB/*antagonists & inhibitors MH - Signal Transduction/*drug effects MH - Stress, Psychological/psychology MH - Swimming/psychology OTO - NOTNLM OT - Brain-derived neurotrophic factor (BDNF) OT - Fluoxetine OT - TLQP62 OT - Tropomyosin-related kinase B OT - VGF-derived peptide OT - cAMP response element-binding protein (CREB) EDAT- 2014/03/19 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/03/18 06:00 PHST- 2013/12/09 00:00 [received] PHST- 2014/02/28 00:00 [revised] PHST- 2014/03/06 00:00 [accepted] PHST- 2014/03/18 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0091-3057(14)00073-2 [pii] AID - 10.1016/j.pbb.2014.03.003 [doi] PST - ppublish SO - Pharmacol Biochem Behav. 2014 May;120:140-8. doi: 10.1016/j.pbb.2014.03.003. Epub 2014 Mar 11.