Abstract
Depression is a multicausal disorder and has been associated with metabolism regulation and immuno-inflammatory reaction. The anorectic molecule nesfatin-1 has recently been characterized as a potential mood regulator, but its precise effect on depression and the possible mechanisms remain unknown, especially when given peripherally. In the present study, nesfatin-1 was intraperitoneally injected to the rats and the depression-like behavior and activity of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated. The plasma concentrations of nesfatin-1, interleukin 6 (IL-6), and C-reactive protein (CRP); and the hypothalamic expression levels of nesfatin-1, synapsin I, and synaptotagmin I mRNA were evaluated in nesfatin-1 chronically treated rats. The results showed that both acute and chronic administration of nesfatin-1 increased immobility in the forced swimming test (FST), and resulted in the hyperactivity of HPA axis, as indicated by the increase of plasma corticosterone concentration and hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Moreover, after chronic nesfatin-1 administration, the rats exhibited decreased activity and exploratory behavior in the open field test (OFT) and increased mRNA expression of synapsin I and synaptotagmin I in the hypothalamus. Furthermore, chronic administration of nesfatin-1 elevated plasma concentrations of IL-6 and CRP, which were positively correlated with despair behavior, plasma corticosterone level, and the hypothalamic mRNA expression of synapsin I and synaptotagmin I. These results indicated that exogenous nesfatin-1 could induce the immune-inflammatory activation, which might be a central hug linking the depression-like behavior and the imbalanced mRNA expression of synaptic vesicle proteins in the hypothalamus.
Highlights
As a metabolic disorder, depression has been associated with anorexigenic or orexigenic peptides (Lang and Borgwardt, 2013; Bali et al, 2014)
We first demonstrated that an intraperitoneal administration of a single dose of nesfatin-1 increased the immobility of rats in the forced swimming test (FST) and induced the hyperactivity of the HPA axis
Together with the fact that chronic administration is a route delivery method in clinic, we explored the effect of chronic nesfatin-1 treatment on the depression-like behavior of rats and the underlying mechanism
Summary
Depression has been associated with anorexigenic or orexigenic peptides (Lang and Borgwardt, 2013; Bali et al, 2014). Nesfatin-1 is a newly discovered anorexigenic factors that cleaved from its precursor nucleobindin 2 (NUCB2; Oh et al, 2006; Stengel et al, 2009). It has been reported that the plasma nesfatin-1 level is statistically higher in patients with major depressive disorder (Ari et al, 2011) and associated with the elevated scores of anxiety and depression (Ari et al, 2011; Hofmann et al, 2013), and intracerebroventricular (ICV) injection of nesfatin-1 could induce anxiety- and fear-related behaviors (Merali et al, 2008). The causality between nesfatin and anxiety or depression-like changes remains unknown, and little is known about the effect of nesfatin-1 on the neuropsychic behaviors when given peripherally
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