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

Astragaloside IV Promotes Adult Neurogenesis in Hippocampal Dentate Gyrus of Mouse through CXCL1/CXCR2 Signaling.
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DOI:
10.3390/molecules23092178
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发表时间:
2018-08-29
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Wu X
Wu X
中科院分区:
其他
文献类型:
--
作者:
Huang F;Lan Y;Qin L;Dong H;Shi H;Wu H;Zou Q;Hu Z;Wu X

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据报道,黄芪甲苷(Astragaloside IV, ASI)可促进体外神经干细胞增殖和中性粒细胞上CXCR2的表达。本研究旨在探讨ASI对小鼠海马齿状回成体神经发生的影响,并探讨其可能的机制。分别计算ASI或给药两周后的增殖细胞(BrdU+)、早熟神经元(DCX+)、早期增殖细胞(BrdU+/DCX+)、增殖放射状胶质样细胞(BrdU+/GFAP+)和新生神经元(BrdU+/NeuN+)总数。结果显示,ASI小鼠DGs中BrdU+细胞和DCX+细胞显著增加。ASI组BrdU+/DCX+、BrdU+/GFAP+、BrdU+/NeuN+细胞数量均升高。相应的,ASI增加了海马DCX、GFAP和NeuN蛋白的表达。进一步研究发现,ASI显著上调海马组织中CXCL1和CXCR2 mRNA和蛋白的表达。ASI对DCX、GFAP和NeuN蛋白表达的促进作用被CXCR2抑制剂SB225002消除。我们的研究结果表明,ASI调节了CXCL1/CXCR2信号通路的稳态,这可能是小鼠海马DGs内神经发生增加的原因。
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.
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