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CRHR1 Mediates the Up-Regulation of Synapsin I Induced by Nesfatin-1 Through ERK 1/2 Signaling in SH-SY5Y Cells

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Abstract

The anorexigenic molecule nesfatin-1 has recently been taken as a potential mood regulator, but the potential mechanisms remain unknown. Results of our previous study have demonstrated that nesfatin-1 could induce anxiety- and depression-like behaviors in rats, accompanied by the hyperactivity of the hypothalamic–pituitary–adrenal axis and the imbalanced mRNA expression of synaptic vesicle proteins. To explore the potential neurobiological mechanism underlying the effect of nesfatin-1 on the synaptic plasticity, the human neuroblastoma SH-SY5Y cells were cultured and treated with different concentrations of nesfatin-1 in the present study. The mRNA and protein expressions of corticotropin-releasing hormone (CRH) were measured via real-time fluorescent quantitative PCR and western blot, respectively. The protein expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated-ERK1/2 (p-ERK1/2), and synapsin I were detected via western blot. The results confirmed that nesfatin-1 (10−9~10−7 mol/L) could up-regulate the expression of CRH. Moreover, nesfatin-1 (10−9~10−7 mol/L) could also increase the protein expressions of p-ERK1/2 and synapsin I, and these effects could be blocked by CP376395, a selective antagonist of CRH type 1 receptor (CRHR1). Furthermore, the increased expression of synapsin I induced by nesfatin-1 could also be reversed by PD98059, a specific inhibitor of the p-ERK. These results indicated that CRHR1 might mediate the effect of nesfatin-1 on the expressions of synapsin I via ERK1/2 signaling pathway.

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Acknowledgement

This project was provided by the Natural Science Foundation of China (81401122), the Natural Science Foundation of Anhui Province of China (1408085MH154), the Training Programme Foundation for the Talents by Anhui Education Commission (KJ2014RC004), and the foundation for Yong Key Teacher of Anhui Medical University (0601020103).

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  1. Zheng Chen and Ya-Yun Xu have contributed equally to this work.

Authors and Affiliations

  1. Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, People’s Republic of China

    Zheng Chen, Jin-Fang Ge & Fei-Hu Chen

  2. Department of pharmacy, The Fourth People’s Hospital in Hefei, 316 Huangshan Road, Hefei, 230032, People’s Republic of China

    Ya-Yun Xu

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  1. Zheng Chen
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Author’s Contribution

Associate Prof. Jin-Fang Ge and Prof. Fei-Hu Chen designed the study, and Prof. Jin-Fang Ge wrote the protocol and the first draft of the manuscript. Dr. Zheng Chen and Dr. Ya-Yun Xu managed the literature searches and the statistical analyses. Zheng Chen and Ya-Yun Xu performed the experiments. All authors contributed to and have approved the final manuscript.

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Correspondence to Jin-Fang Ge.

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Chen, Z., Xu, YY., Ge, JF. et al. CRHR1 Mediates the Up-Regulation of Synapsin I Induced by Nesfatin-1 Through ERK 1/2 Signaling in SH-SY5Y Cells. Cell Mol Neurobiol 38, 627–633 (2018). https://doi.org/10.1007/s10571-017-0509-x

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