Astragalus polysaccharides promote neural stem cells-derived oligodendrogenesis through attenuating CD8⁺T cell...

Endogenous neural stem cells (NSCs) have the potential to generate remyelinating oligodendrocytes, which play an important role in multiple sclerosis (MS). However, the differentiation of NSCs into oligodendrocytes is insufficient, which is considered a major cause of remyelination failure. Our previous work reported that Astragalus polysaccharides (APS) had a neuroprotective effect on experimental autoimmune encephalomyelitis (EAE) mice. However, it remains unclear whether APS regulate NSCs differentiation in EAE mice. In this study, our data illustrated that APS administration could promote NSCs in the subventricular zone (SVZ) to differentiate into oligodendrocytes. Furthermore, we found that APS significantly improved neuroinflammation and inhibited CD8⁺T cell infiltration into SVZ of EAE mice. We also found that MOG_35-55-specific CD8⁺T cells suppressed NSCs differentiation into oligodendrocytes by secreting IFN-γ, and APS facilitated the differentiation of NSCs into oligodendrocytes which was related to decreased IFN-γ secretion. In addition, APS treatment did not show a better effect on the NSCs-derived oligodendrogenesis after CD8⁺T cell depletion. This present study demonstrated that APS alleviated neuroinflammation and CD8⁺T cell infiltration into SVZ to induce oligodendroglial differentiation, and thus exerted neuroprotective effect. Our findings revealed that reducing the infiltration of CD8⁺T cells might contribute to enhancing NSCs-derived neurogenesis. And APS might be a promising drug candidate to treat MS.