Abstract
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.
Highlights
Adult hippocampal neurogenesis attracts specific attention as it is suggested to play an important role in higher cognitive function, most notably memory processes, and certain affective behaviors [1].Lateral ventricles and hippocampal dentate gyrus (DG) are the well-known regions in the brain where the neural progenitor cells proliferate and differentiate into mature neurons throughout the lifetime of animals [2,3]
These results indicated that Astragaloside IV (ASI) increased proliferative cells, pre-mature neurons and early proliferative cells
These results indicated that ASI increased proliferative gila-like cells gila-like cells and newly generated neurons in the subgranular zone (SGZ)
Summary
Adult hippocampal neurogenesis attracts specific attention as it is suggested to play an important role in higher cognitive function, most notably memory processes, and certain affective behaviors [1].Lateral ventricles and hippocampal dentate gyrus (DG) are the well-known regions in the brain where the neural progenitor cells proliferate and differentiate into mature neurons throughout the lifetime of animals [2,3]. The mature neurons can consolidate surrounding structures and participate in many critical processes such as learning and memory [4]. Accumulative evidence shows that adult neurogenesis is essential for specific types of hippocampus-dependent learning [5,6,7]. Chemokines (chemotactic cytokines) compose a family of small protein ligands involved in leukocyte migration and communication [8]. Chemokines and their receptors are expressed in all major types of cells in the central nervous system (CNS), and a growing body of evidence suggests that chemokines and their receptors mediate the cellular communication in CNS [9]. CXCR2 has been shown to enhance the survival of hippocampal neurons [10,11], and is involved in patterning the spinal cord by controlling the position of oligodendrocyte precursors after stimulation by its ligand CXCL1 [12]
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