Artesunate Mitigates Cognitive Deficits by Promoting Hippocampal Neural Stem/Progenitor Cells Proliferation and Neurogenesis in Cadmium-Exposed Mice

Abstract Cadmium is a toxic heavy metal which could cause central nervous system damage and cognitive dysfunction. However, the effective therapy strategy for cadmium-caused cognitive dysfunction had not been established. In present study, we investigated the therapeutic effect of artesunate on cadmium induced cognitive deficits and neural stem/progenitor cells (NSPCs) proliferation as well as neurogenesis inhibition. Male mice were injected with cadmium chloride (1mg/Kg) for 4weeks, followed with 4 weeks of artesunate (50mg/Kg). Cadmium chloride and artesunate were used to treat NSPCs in vitro. Subsequently, the learning and memory function of mice were detected by Y-maze and Morris water maze tests and NSPCs proliferation and neurogenesis were examined by western blots and immunofluorescence. The results showed cadmium impaired mice cognitive severity. And cadmium significantly inhibited the proliferation and neurogenesis of NSPCs in hippocampi and in vitro. Moreover, cadmium reduced the expression of phosphorylated AKT. However, artesunate reversed the cadmium-induced cognitive deficits as well as the inhibition of NSPCs proliferation and neurogenesis. Additionally, artesunate increased the phosphorylation of AKT in hippocampi and NSPCs. Our data manifested artesunate could reverse cadmium-induced mice cognitive deficits and reduce the inhibition of cadmium on NSPCs proliferation and neurogenesis via PI3K-AKT pathway.