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Open AccessArticle

Neuropeptide Trefoil Factor 3 Reverses Depressive-Like Behaviors by Activation of BDNF-ERK-CREB Signaling in Olfactory Bulbectomized Rats

by Jiali Li 1,2,3, Yixiao Luo 1, Ruoxi Zhang 1,2,3, Haishui Shi 1, Weili Zhu 1,2,3,* and Jie Shi 1,2,3,4,5,*
1
National Institute on Drug Dependence, Peking University, Beijing 100191, China
2
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
3
Beijing Key Laboratory on Drug Dependence Research, Beijing 100191, China
4
The State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China
5
Key Laboratory for Neuroscience of the Ministry of Education and Ministry of Public Healthy, Beijing 100191, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Domenico de Berardis and Michele Fornaro
Int. J. Mol. Sci. 2015, 16(12), 28386-28400; https://doi.org/10.3390/ijms161226105
Received: 21 October 2015 / Revised: 16 November 2015 / Accepted: 17 November 2015 / Published: 30 November 2015
(This article belongs to the Special Issue Antipsychotics)
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. View Full-Text
Keywords: TFF3; olfactory bulbectomy; depression; BDNF; ERK; CREB TFF3; olfactory bulbectomy; depression; BDNF; ERK; CREB
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Li, J.; Luo, Y.; Zhang, R.; Shi, H.; Zhu, W.; Shi, J. Neuropeptide Trefoil Factor 3 Reverses Depressive-Like Behaviors by Activation of BDNF-ERK-CREB Signaling in Olfactory Bulbectomized Rats. Int. J. Mol. Sci. 2015, 16, 28386-28400.

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