Remyelination is enhanced by Astragalus polysaccharides through inducing the differentiation of oligodendrocytes from neural stem cells in cuprizone model of demyelination.

ABSTRACT

Demyelination is the hallmark of multiple sclerosis (MS). Promoting remyelination is an important strategy to treat MS. Our previous study showed that Astragalus polysaccharides (APS), the main bioactive component of Astragalus membranaceus, could prevent demyelination in experimental autoimmune encephalomyelitis mice. To investigate the effects of APS on remyelination and the underlying mechanisms, in this study we set up a cuprizone-induced demyelination model in mice and treated them with APS. It was found that APS relieved the neurobehavioral dysfunctions caused by demyelination, and efficaciously facilitated remyelination in vivo. In order to determine whether the mechanism of enhancing remyelination was associated with the differentiation of neural stem cells (NSCs), biomarkers of NSCs, astrocytes, oligodendrocytes and neurons were measured in the corpus callosum tissues of mice through Real-time PCR, Western blot and immunohistochemistry assays. Data revealed that APS suppressed the stemness of NSCs, reduced the differentiation of NSCs into astrocytes, and promoted the differentiation into oligodendrocytes and neurons. This phenomenon was confirmed in the differentiation model of C17.2 NSCs cultured in vitro. Since Sonic hedgehog signaling pathway has been proven to be crucial to the differentiation of NSCs into oligodendrocytes, we examined expression levels of the key molecules in this pathway in vivo and in vitro, and eventually found APS activated this signaling pathway. Together, our results demonstrated that APS probably activated Sonic hedgehog signaling pathway first, then induced NSCs to differentiate into oligodendrocytes and promoted remyelination, which suggested that APS might be a potential candidate in treating MS.