title: The VGF-derived peptide TLQP62 produces antidepressant-like effects in mice via the BDNF/TrkB/CREB signaling pathway.
abstract: 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 α1-adrenoceptor antagonist prazosin, the β 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.
authors.affiliation: 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.
authors.forename: Peipei
authors.initials: P
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: No. 97 Hospital, Xuzhou, Jiangsu 221000, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Siyun
authors.initials: S
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Huihui
authors.initials: H
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors*; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors*; D003866:Depressive Disorder / Q000188:drug therapy / Q000523:psychology; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D020813:Receptor, trkB / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000523:psychology; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D009479:Neuropeptides; D010455:Peptides; C000593377:TLQP62 peptide; C522413:VGF peptide; D020813:Receptor, trkB
keywords: Brain-derived neurotrophic factor (BDNF); Fluoxetine; TLQP62; Tropomyosin-related kinase B; VGF-derived peptide; cAMP response element-binding protein (CREB)