Xanthoceraside modulates neurogenesis to ameliorate cognitive impairment in APP/PS1 transgenic mice

Neuronal loss is reported to be an important pathological process in Alzheimer's disease (AD). Neurogenesis is a process of generation of new neurons to fill the neuronal loss. Xanthoceraside has been shown to attenuate the cognitive deficits in several AD animal models. However, little is known about the effect of xanthoceraside on neurogenesis in APP/PS1 transgenic mice. Thus, in this study, we investigated whether xanthoceraside can ameliorate learning and memory impairment by promoting NSCs proliferation and neuronal differentiation. The results suggested that xanthoceraside significantly ameliorated the cognitive impairment and induced NSCs proliferation and neuronal differentiation in APP/PS1 transgenic mice. Meanwhile, in vitro study revealed that xanthoceraside increased the size of NSCs and induced NSCs differentiation into neurons compared with amyloid beta-peptide (25-35) (Aβ_25-35) treatment. Furthermore, we found that xanthoceraside significantly increased the expression of Wnt3a and p-GSK3β, decreased the expression of p-β-catenin, and induced nuclear translocation of β-catenin in APP/PS1 transgenic mice. Furthermore, in vitro study found that the effect of xanthoceraside on inducing NSCs proliferation and neuronal differentiation were inhibited by Wnt pathway inhibitor Dickkopf-1 (Dkk-1). Our data demonstrated that xanthoceraside may promote the proliferation and differentiation of NSCs into neurons by up-regulating the Wnt/β-catenin pathway to fill the neuronal loss, thereby improving learning and memory impairment in APP/PS1 transgenic mice.