Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer's Disease Rat Models.

Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer's Disease Rat Models.
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DOI:
10.1155/2016/3106980
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发表时间:
2016
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Yanwu X
Yanwu X
中科院分区:
其他
文献类型:
--
作者:
Haiyan H;Rensong Y;Guoqin J;Xueli Z;Huaying X;Yanwu X

文献摘要

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干细胞治疗是治疗神经退行性疾病如阿尔茨海默病(AD)的一种很有前途的治疗策略。然而,内源性祖细胞或移植干细胞在病理环境中维持更新和替代能力的机制仍然是一个谜。为了研究黄芪甲苷(ASI)对移植神经干细胞(NSCs)增殖和分化的影响,我们从E14大鼠胚胎海马中培养NSCs,用ASI处理后将其移植到AD模型大鼠海马中。体外实验表明,10−5 M ASI诱导NSCs分化为β-微管蛋白III+和GFAP+细胞。将NSCs移植到大鼠AD模型中可以改善学习和记忆,特别是在asi治疗组。ASI治疗导致海马中β-微管蛋白III+细胞数量增加。进一步研究表明,ASI在体外和体内均能抑制PS1的表达。高剂量ASI下调Notch细胞内结构域,而低剂量ASI增加Notch-1和NICD。综上所述,ASI处理部分通过Notch信号通路促进NSC增殖和分化,从而改善AD模型的学习和记忆。
Stem cell-based therapy is a promising treatment strategy for neurodegenerative diseases such as Alzheimer's disease (AD). However, the mechanism underlying the maintenance of renewal and replacement capabilities of endogenous progenitor cells or engrafted stem cells in a pathological environment remains elusive. To investigate the effect of astragaloside IV (ASI) on the proliferation and differentiation of the engrafted neural stem cells (NSCs), we cultured NSCs from the hippocampus of E14 rat embryos, treated the cells with ASI, and then transplanted the cells into the hippocampus of rat AD models. In vitro experimentation showed that 10−5 M ASI induced NSCs to differentiate into β-tubulin III+ and GFAP+ cells. NSCs transplantation into rat AD models resulted in improvements in learning and memory, especially in the ASI-treated groups. ASI treatment resulted in an increase in the number of β-tubulin III+ cells in the hippocampus. Further investigation showed that ASI inhibited PS1 expression in vitro and in vivo. The high-dose ASI downregulated the Notch intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In conclusion, ASI treatment resulted in improvements in learning and memory of AD models by promoting NSC proliferation and differentiation partly through the Notch signal pathway.