The leptin/BDNF/TrkB signaling pathway improves corticosteroid combined with chronic restraint stress-induced depressive-like behavior in mice

Abstract

This study explored the effect and mechanism of leptin on depressive-like behavior induced by chronic corticosterone injections combined with chronic restraint stress (CORT-CRS) in mice. Differentially expressed genes (DEGs) were extracted using the Gene Expression Omnibus database and Sangerbox tool. Construct protein–protein interaction networks of target DEGs using Cytoscape software, and hub genes brain-derived neurotrophic factor (BDNF) were identified. A mouse model of depression was established using CORT-CRS. Behavioral changes were detected in the mice using the tail suspension, forced swimming, sugar water preference (SPT), and open field tests (OFT). Serum inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein expression levels of BDNF and tyrosine kinase receptor B (TrkB). Immunofluorescence was used to detect hippocampal neurogenesis in each mouse group. Compared with the control group, mice in the CORT-CRS group presented with marked depression-like behavior and a higher interleukin (IL) -6, IL-1 β, tumor necrosis factor alpha (TNF – α) concentration. Different doses of leptin reversed depressive-like behavior in the CORT-CRS model mice, with significantly increased levels of BDNF, TrkB protein expression (P < 0.01).

Furthermore, leptin promoted hippocampal neurogenesis in CORT-CRS-treated mice in vivo. Consequently, leptin alleviates CORT-CRS-induced depression-like behavior in mice by stimulating hippocampal neurogenesis. One possible mechanism could be related to the activation of the BDNF/TrkB signaling pathway, which could pave way for novel therapeutic targets that can be explored to prevent and treat depression.