PMID- 26633367 OWN - NLM STAT- MEDLINE DCOM- 20160920 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 16 IP - 12 DP - 2015 Nov 30 TI - Neuropeptide Trefoil Factor 3 Reverses Depressive-Like Behaviors by Activation of BDNF-ERK-CREB Signaling in Olfactory Bulbectomized Rats. PG - 28386-400 LID - 10.3390/ijms161226105 [doi] AB - The trefoil factors (TFFs) are a family of three polypeptides, among which TFF1 and TFF3 are widely distributed in the central nervous system. Our previous study indicated that TFF3 was a potential rapid-onset antidepressant as it reversed the depressive-like behaviors induced by acute or chronic mild stress. In order to further identify the antidepressant-like effect of TFF3, we applied an olfactory bulbectomy (OB), a classic animal model of depression, in the present study. To elucidate the mechanism underlying the antidepressant-like activity of TFF3, we tested the role of brain-derived neurotrophic factor (BDNF)-extracellular signal-related kinase (ERK)-cyclic adenosine monophosphate response element binding protein (CREB) signaling in the hippocampus in the process. Chronic systemic administration of TFF3 (0.1 mg/kg, i.p.) for seven days not only produced a significant antidepressant-like efficacy in the OB paradigm, but also restored the expression of BDNF, pERK, and pCREB in the hippocampal CA3. Inhibition of BDNF or extracellular signal-related kinase (ERK) signaling in CA3 blocked the antidepressant-like activity of TFF3 in OB rats. Our findings further confirmed the therapeutic effect of TFF3 against depression and suggested that the normalization of the BDNF-ERK-CREB pathway was involved in the behavioral response of TFF3 for the treatment of depression. FAU - Li, Jiali AU - Li J AD - National Institute on Drug Dependence, Peking University, Beijing 100191, China. lijiali@bjmu.edu.cn. AD - Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. lijiali@bjmu.edu.cn. AD - Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. lijiali@bjmu.edu.cn. FAU - Luo, Yixiao AU - Luo Y AD - National Institute on Drug Dependence, Peking University, Beijing 100191, China. luoyx@bjmu.edu.cn. FAU - Zhang, Ruoxi AU - Zhang R AD - National Institute on Drug Dependence, Peking University, Beijing 100191, China. zrx@bjmu.edu.cn. AD - Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. zrx@bjmu.edu.cn. AD - Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. zrx@bjmu.edu.cn. FAU - Shi, Haishui AU - Shi H AD - National Institute on Drug Dependence, Peking University, Beijing 100191, China. shhsh001@bjmu.edu.cn. FAU - Zhu, Weili AU - Zhu W AD - National Institute on Drug Dependence, Peking University, Beijing 100191, China. zhu_wl@bjmu.edu.cn. AD - Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. zhu_wl@bjmu.edu.cn. AD - Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. zhu_wl@bjmu.edu.cn. FAU - Shi, Jie AU - Shi J AD - National Institute on Drug Dependence, Peking University, Beijing 100191, China. shijie@bjmu.edu.cn. AD - Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. shijie@bjmu.edu.cn. AD - Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. shijie@bjmu.edu.cn. AD - The State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China. shijie@bjmu.edu.cn. AD - Key Laboratory for Neuroscience of the Ministry of Education and Ministry of Public Healthy, Beijing 100191, China. shijie@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151130 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Neuropeptides) RN - 0 (TFF3 protein, rat) RN - 0 (Trefoil Factor-3) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Antidepressive Agents/administration & dosage/pharmacology MH - Behavior, Animal/*drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Depression/drug therapy/etiology/*metabolism MH - Disease Models, Animal MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Hippocampus/drug effects/metabolism MH - Male MH - Neuropeptides/administration & dosage/*pharmacology MH - Olfactory Bulb/surgery MH - Phosphorylation MH - Rats MH - Receptor, trkB/antagonists & inhibitors MH - Signal Transduction/*drug effects MH - Trefoil Factor-3 PMC - PMC4691052 OTO - NOTNLM OT - BDNF OT - CREB OT - ERK OT - TFF3 OT - depression OT - olfactory bulbectomy EDAT- 2015/12/04 06:00 MHDA- 2016/09/22 06:00 PMCR- 2015/12/01 CRDT- 2015/12/04 06:00 PHST- 2015/10/21 00:00 [received] PHST- 2015/11/16 00:00 [revised] PHST- 2015/11/17 00:00 [accepted] PHST- 2015/12/04 06:00 [entrez] PHST- 2015/12/04 06:00 [pubmed] PHST- 2016/09/22 06:00 [medline] PHST- 2015/12/01 00:00 [pmc-release] AID - ijms161226105 [pii] AID - ijms-16-26105 [pii] AID - 10.3390/ijms161226105 [doi] PST - epublish SO - Int J Mol Sci. 2015 Nov 30;16(12):28386-400. doi: 10.3390/ijms161226105.