Astragaloside IV Promotes Adult Neurogenesis in Hippocampal Dentate Gyrus of Mouse through CXCL1/CXCR2 Signaling

Astragaloside IV (ASI) has been reported to promote neural stem cells proliferation in vitro and CXCR2 expression on neutrophils. The present study was aimed to investigate the influence of ASI on adult neurogenesis in hippocampal dentate gyrus (DGs) of mouse and to discuss the possible underlying mechanisms. Total number of proliferative cells (BrdU(+)), pre-mature neurons (DCX+), early proliferative cells (BrdU(+)/DCX+), proliferative radial gila-like cells (BrdU(+)/GFAP(+)) and newly generated neurons (BrdU(+)/NeuN(+)) after ASI or vehicle administration for two weeks were counted, respectively. The results showed that BrdU(+) cells and DCX+ cells were significantly increased in DGs of mice administered with ASI. The numbers of BrdU(+)/DCX+, BrdU(+)/GFAP(+) cells and BrdU(+)/NeuN(+) cells were also elevated in the ASI group. Correspondingly, ASI increased the protein expression of hippocampal DCX, GFAP and NeuN. Further study disclosed that ASI remarkably up-regulated the mRNA and protein expressions of CXCL1 as well as that of CXCR2 in the hippocampus. The promotive effect of ASI on DCX, GFAP and NeuN protein expression was abolished by SB225002, the inhibitor of CXCR2. Our results indicated that ASI modulated the homeostasis of the CXCL1/CXCR2 signaling pathway, which might be responsible for the increased neurogenesis within the hippocampal DGs of mice.