Ginseng Total Saponins Reverse Corticosterone-Induced Changes in Depression-Like Behavior and Hippocampal Plasticity-Related Proteins by Interfering with GSK-3β-CREB Signaling Pathway

This study aimed to explore the antidepressant mechanisms of ginseng total saponins (GTS) in the corticosterone-induced mouse depression model. In Experiment 1, GTS (50, 25, and 12.5 mg kg(-1) d(-1), intragastrically) were given for 3 weeks. In Experiment 2, the same doses of GTS were administrated after each corticosterone (20 mg kg(-1) d(-1), subcutaneously) injection for 22 days. In both experiments, mice underwent a forced swimming test and a tail suspension test on day 20 and day 21, respectively, and were sacrificed on day 22. Results of Experiment 1 revealed that GTS (50 and 25 mg kg(-1) d(-1)) exhibited antidepressant activity and not statistically altered hippocampal protein levels of brain-derived neurotrophic factor (BDNF) and neurofilament light chain (NF-L). Results of Experiment 2 showed that GTS (50 and 25 mg kg(-1) d(-1)) ameliorated depression-like behavior without normalizing hypercortisolism. The GTS treatments reversed the corticosterone-induced changes in mRNA levels of BDNF and NF-L, and protein levels of BDNF NF-L, phosphor-cAMP response element-binding protein (Ser133), and phosphor-glycogen synthase kinase-3 beta (Ser9) in the hippocampus. These findings imply that the effect of GTS on corticosterone-induced depression-like behavior may be mediated partly through interfering with hippocampal GSK-3 beta-CREB signaling pathway and reversing decrease of some plasticity-related proteins.