Depression-like Behavior Induced by Nesfatin-1 in Rats: Involvement of Increased Immune Activation and Imbalance of Synaptic Vesicle Proteins

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.

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC

“…Moreover, the elevated plasma concentrations of CRP and IL-6 in patients with major depressive disorder are reported to be positively related to the increased plasma nesfatin-1 level (Xia et al, 2018), which is an anorexigenic molecule localized widely in the brain and peripheral tissues with multiple biological activities including regulation of feeding and mood (Weibert et al, 2019). Consistently, in our previous study (Ge et al, 2015a), administration with nesfatin-1 could induce depression-like behaviors, accompanied with the increased plasma concentrations of IL-6 and CRP. Moreover, the antidepressant-like effect of ibuprofen, which is one of the common used nonsteroidal anti-inflammatory drugs (NSAIDs), has demonstrated in animal studies (Mesripour et al, 2019;Seo et al, 2019).…”

Xiaoyaosan Ameliorates Chronic Immobilization Stress-Induced Depression-Like Behaviors and Anorexia in Rats: The Role of the Nesfatin-1–Oxytocin–Proopiomelanocortin Neural Pathway in the Hypothalamus

“…After exposure to CIS, the expression of NES1-positive neurons in the PVN was significantly increased, while there was no significant difference in the expression of NES1-positive neurons in the ARC. Our observation that CIS upregulated NES1 expression in the PVN, which is correlated with depression-like conditions in rats, further confirms the pro-depressive role of NES1 (35).…”

High levels of Nesfatin-1 in relation to the dysfunction of the hypothalamic–pituitary–adrenal and hypothalamus–pituitary–thyroid axes in depressed patients with subclinical hypothyroidism

“…Apart from the findings that Nesfatin-1 is distributed in stress-related brain regions, including the hypothalamus, and colocalized with stress-related substances,18,19 intracerebroventricular administration of Nesfatin-1 has been reported to be able to activate the hypothalamic–pituitary–adrenal (HPA) axis, the hyperactivity of which is proposed to be among the causal factors for triggering depressive episodes 20. Similarly, the results of our previous study confirmed that intraperitoneal administration of Nesfatin-1 in a single dose or chronically resulted in depression-like behavior and HPA axis hyperactivity in rats 21. Furthermore, an increased plasma concentration of Nesfatin-1 and an increased hypothalamic mRNA expression of Nesfatin-1 have been observed in animal models of depression 22.…”