title: Neuropeptide Trefoil Factor 3 Reverses Depressive-Like Behaviors by Activation of BDNF-ERK-CREB Signaling in Olfactory Bulbectomized Rats.
abstract: 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.
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China. lijiali@bjmu.edu.cn.|Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. lijiali@bjmu.edu.cn.|Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. lijiali@bjmu.edu.cn.
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China. luoyx@bjmu.edu.cn.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Luo
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China. zrx@bjmu.edu.cn.|Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. zrx@bjmu.edu.cn.|Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. zrx@bjmu.edu.cn.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Zhang
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China. shhsh001@bjmu.edu.cn.
authors.forename: Haishui
authors.initials: H
authors.lastname: Shi
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China. zhu_wl@bjmu.edu.cn.|Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. zhu_wl@bjmu.edu.cn.|Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. zhu_wl@bjmu.edu.cn.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhu
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China. shijie@bjmu.edu.cn.|Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. shijie@bjmu.edu.cn.|Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China. shijie@bjmu.edu.cn.|The State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China. shijie@bjmu.edu.cn.|Key Laboratory for Neuroscience of the Ministry of Education and Ministry of Public Healthy, Beijing 100191, China. shijie@bjmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000601:surgery; D010766:Phosphorylation; D051381:Rats; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D000071165:Trefoil Factor-3
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D009479:Neuropeptides; C099037:TFF3 protein, rat; D000071165:Trefoil Factor-3; D020813:Receptor, trkB; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BDNF; CREB; ERK; TFF3; depression; olfactory bulbectomy