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

International Journal of Molecular Sciences

Jiali Li²  Yixiao Luo²  Ruoxi Zhang²  Haishui Shi²  Weili Zhu²  Jie Shi²  Domenico de Berardis¹ 

[1] National Institute on Drug Dependence, Peking University, Beijing 100191, ChinaNational Institute on Drug Dependence, Peking University, Beijing 100191, China;

关键词: TFF3;    olfactory bulbectomy;    depression;    BDNF;    ERK;    CREB;   

DOI  :  10.3390/ijms161226105

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.