[Saikosaponin B2 improves depressive behavior of VaD mice by promoting oligodendrocyte maturation via regulating Akt/mTOR pathway].

The aim of this study is to investigate whether saikosaponin B2(SSB2) promotes oligodendrocyte maturation and myelination by activating protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway to improve the depression phenotype associated with vascular dementia(VaD). C57BL/6 mice were used as the research subjects. The VaD depression model was established by bilateral common carotid artery stenosis(BCAS) combined with chronic restraint stress(CRS). There were sham group, SSB2 group, BCAS/CRS group, and BCAS/CRS+SSB2 group. Depression-like behavior was assessed using the forced swim test and the tail suspension test. HE staining and TUNEL staining were used to observe the pathology and apoptosis of the corpus callosum. Immunofluorescence was used to detect the number of CC1~+ mature oligodendrocytes. Western blot was used to analyze the expression of myelin related proteins [myelin basic protein(MBP), myelin oligodendrocyte glycoprotein(MOG), myelin associated glycoprotein(MAG)], p-Akt, and p-mTOR. In vitro, primary oligodendrocyte precursor cells(OPCs) were treated with different concentrations of SSB2. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was used to detect cell viability, and Western blot was used to detect the changes in the above proteins. The results showed that SSB2 significantly ameliorated BCAS/CRS-induced depression-like behavior and myelin structure damage in the corpus callosum of mice, increased the number of CC1~+ cells and the expression of myelin-related proteins, and activated the Akt/mTOR pathway. In vitro experiments further confirmed that SSB2 could increase the expression of MBP, MOG, MAG and the levels of p-Akt and p-mTOR in OPCs in a dose-dependent manner, and had no effect on cell viability. In conclusion, SSB2 may promote oligodendrocyte maturation and myelin repair by activating the Akt/mTOR signaling pathway, thus improving VaD related depressive behavior. This finding provides a new theoretical basis for the prevention and treatment of VaD comorbid depression.