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

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.

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

“…The mechanism underlying of neurological outcomes improvement by As IV from stroke may be due to enhanced NSCs' proliferation and neurogenesis through activating multiple signaling pathways as reported in previous studies (Yang et al, 2017;Huang et al, 2018;Chen X. et al, 2019). As IV may facilitate the host brain neurogenesis by stimulating and activating the quiesent stem cells in hippocampus.…”

“…It has been shown that As IV can not only enhance adult hippocampal neurogenesis (Huang et al, 2018), but also promote NSC proliferation and neurogenesis in transiently ischemic cerebral brains after stroke (Chen X. et al, 2019). In this study, As IV promoted the expression of the DCX, BrdU, and Sox2 proteins in the subgranular zone (SGZ) after stroke in vivo (Figures 2A-D).…”

“…Astragaloside IV (As IV), a primary bioactive compound of Radix Astragali: Astragalus mongholicus Bunge (Fabaceae), has beneficial effect on ameliorating cognitive deficits after stroke through its anti-oxidant, anti-inflammatory, and anti-apoptosis properties (Li et al, 2019;Xue et al, 2019;. Furthermore, it has been found that As IV could enhance adult hippocampal neurogenesis (Yang et al, 2017;Huang et al, 2018) and promote neural stem cells (NSCs) proliferation in transiently ischemic cerebral brains (Chen X. et al, 2019). So As IV could be a promising strategy in the therapeutic arsenal against ischemic stroke for its ameliorating cognitive defi cits and promoting neurogenesis.…”

Neuroinflammation and Neurogenesis in Alzheimer’s Disease and Potential Therapeutic Approaches

“…Moreover, long-term peripheral LPS injections for 28 days in adult mice had a long-term negative impact on AHN [121]. In addition to the effect of microglia and the duration of inflammation, some cytokines or chemokines, such as IL-1α, IL-6, IL-10, CX3CL1, CXCL1, and CXCL12 have important roles in positively regulating neurogenesis [124][125][126][127][128][129][130]. The proinflammatory cytokines released by activated microglia or astrocytes, such as IL-1β, TNF-α, IL-18, and IFN-γ, and some chemokines, such as CCL11, negatively impact the proliferation or differentiation of NSCs [131][132][133][134].…”

“…However, there is as yet no direct evidence regarding the impact of exercise on neuroinflammation and neurogenesis in AD animal models. Parachikova et al [217] reported that voluntary exercise in Tg2576 aged mice not only improved their spatial learning ability but also increased hippocampal expression of CXCL1 and CXCL12, which have been reported to have proneurogenic effects [129,130]. Nichol et al [218,219] also reported that exercise reduced the expression of TNF-α and IL-1β in the hippocampus of aged Tg2576 mice.…”