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

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.

journal_name

Cell Mol Neurobiol

authors

Chen Z,Xu YY,Ge JF,Chen FH

doi

10.1007/s10571-017-0509-x

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

627-633

issue

3

eissn

0272-4340

issn

1573-6830

pii

10.1007/s10571-017-0509-x

journal_volume

38

pub_type

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