Gastrodin Restores Myelination in the Medial Prefrontal Cortex to Alleviate Depression-Like Behaviors via Inhibiting the Notch and β-Catenin Pathways in the Chronic Restraint Stressed Mouse Model

Abstract

Background: Myelination defects in the medial prefrontal cortex (mPFC) have been linked to depression-like behaviors in mice. Gastrodin (GAS) has been identified as a pro-myelinating drug and has demonstrated anti-depressant potential in depression models. This study aimed to evaluate the roles and possible mechanisms of GAS in regulating depressive behaviors and myelination in a chronic restraint stress (CRS) mouse model. Methods: A CRS protocol was implemented to induce depression-like behaviors in mice. Myelination in the mPFC of CRS mice was assessed by analyzing the expression of myelin proteins and examining the ultrastructure of the myelin sheath. GAS and clemastine fumarate (CF) were administered to CRS mice to investigate their effects on depression-like behaviors and myelin restoration. Additionally, the activities of Notch and β-catenin pathways were assessed using western blot analysis. Results: CRS resulted in depression-like behaviors in 75% of stressed mice (labeled as ‘De’ mice), accompanied by hypomyelination in the mPFC. Treatments with GAS and CF in the ‘De’ mice ameliorated depression-like behaviors and restored myelination in the mPFC. GAS treatment in the ‘De’ mice suppressed the activity of the Notch and β-catenin pathways, while CF treatment in the ‘De’ mice only inhibited the β-catenin pathway. Conclusions: GAS restored myelination in the mPFC, alleviating depression-like behaviors in CRS-induced ‘De’ mice. These effects may be attributed to the inhibition of the Notch and β-catenin pathway activity by GAS.