BDNF-GSK-3β-β-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects of Morinda officinalis Oligosaccharides in Rats

Background: Morinda officinalis oligosaccharides (MOs) have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test (FST) in mice. However, the mechanisms that underlie the antidepressant-like effects of MOs are unclear. Methods: Chronic unpredictable stress (CUS) and FST were used to explore the antidepressant-like effects of MOs and resilience to stress in rats. The PI3K inhibitor LY294002 was microinjected in the medial prefrontal cortex (mPFC) to explore the role of GSK-3β in the antidepressant-like effects of MOs. The expression of brain-derived neurotrophic factor (BDNF), phosphorylated-Ser9-glycogen synthase kinase 3β (GSK-3β), β-catenin, and synaptic proteins was determined in the mPFC and the orbitofrontal cortex (OFC) by Western blot. Results: We found that MOs effectively ameliorated CUS-induced depression-like behaviors in the sucrose preference test (SPT) and FST. The MOs also significantly rescued CUS-induced abnormalities in the BDNF-GSK-3β-β-catenin pathway and synaptic protein deficits in the mPFC but not OFC. The activation of GSK-3β by the PI3K inhibitor LY294002 abolished the antidepressant-like effects of MOs in the FST. Naive rats that were treated with MOs exhibited resilience to CUS, accompanied by increases in the expression of BDNF, phosphorylated-Ser9-GSK-3β, and β-catenin in the mPFC. Conclusion: Our findings indicate that the BDNF-GSK-3β-β-catenin pathway in the mPFC may underlie the antidepressant-like effect of MOs and resilience to stress.