title: 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.
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University Anhui, China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Ge
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University Anhui, China.
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Xu
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University Anhui, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Qin
authors.affiliation: Department of Clinical Medicine, The Second Clinical College of Anhui Medical University Anhui, China.
authors.forename: Yao-Nan
authors.initials: YN
authors.lastname: Peng
authors.affiliation: Department of Clinical Medicine, The Second Clinical College of Anhui Medical University Anhui, China.
authors.forename: Chao-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Department of Clinical Medicine, The Second Clinical College of Anhui Medical University Anhui, China.
authors.forename: Xing-Rui
authors.initials: XR
authors.lastname: Liu
authors.affiliation: Department of Clinical Medicine, The Second Clinical College of Anhui Medical University Anhui, China.
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Liang
authors.affiliation: Department of Clinical Medicine, The Second Clinical College of Anhui Medical University Anhui, China.
authors.forename: Zhong-Zheng
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University Anhui, China.
authors.forename: Fei-Hu
authors.initials: FH
authors.lastname: Chen
keywords: C-reactive protein (CRP); depression; hypothalamic-pituitary-adrenal axis (HPA); interleukin 6 (IL-6); nesfatin-1; synapsin I; synaptotagmin I