期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 120, 期 -, 页码 140-148出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2014.03.003
关键词
VGF-derived peptide; Tropomyosin-related kinase B; Brain-derived neurotrophic factor (BDNF); cAMP response element-binding protein (CREB); TLQP62; Fluoxetine
资金
- National Natural Science Foundation of China [81201050, 30901802, 81000599]
- Natural Science Foundation of Zhejiang province [LQ12H09001, LY12H09002]
- Natural Science Foundation of Ningbo [2012A610249, 2012A610252]
- Innovative Research Team of Ningbo [2009B21002]
- Natural Science Foundation of Ningbo University [XKL11D2111]
- Student Research and Innovation Program (SRIP) of Ningbo University
- K.C. Wong Magna fund of Ningbo University
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 alpha(1)-adrenoceptor antagonist prazosin, the 13 receptor antagonist propranolol, or the D-2 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 (10 mg/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. (C) 2014 Elsevier Inc. All rights reserved.
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