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Sox2在NT-3促进大鼠神经干细胞分化中的作用

, PP. 304-309

Keywords: NT-,Sox,神经干细胞,分化,PIK/AKT信号通路

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Abstract:

目的探讨Sox2在神经营养因子3(neurotrophin-3,NT-3)促进原代大鼠神经干细胞(neuralstemcells,NSCs)分化中的作用及其机制。方法选取孕14~15dSD胎鼠,培养原代脑源性NSCs。观察NT-3对NSCs中Sox2表达及NSCs分化的影响:采用不同浓度NT-3(25、50、100ng/mL)刺激NSCs24h后,检测Sox2、DCX、Olig2、GFAP蛋白的表达量。探索NT-3对Sox2产生影响的机制:使用PI3K/AKT通路阻断剂(10μmol/LLY294002)选择性阻断NT-3的作用后,检测AKT、p-AKT和Sox2在蛋白水平表达量的变化。结果随着NT-3浓度的升高,NSCs中Sox2蛋白水平的表达明显上调(P<0.05),各NT-3处理组的NSCs向神经元前体细胞分化的比例明显增加(P<0.05),100ng/mLNT-3组效果最强,呈现出明显的剂量依赖性;与对照组相比,100ng/mLNT-3组的p-AKT及Sox2蛋白水平显著上调(P<0.05),且LY294002可阻断此作用(P<0.05)。结论NT-3能够上调NSCs中Sox2的表达,后者进而诱导NSCs向神经元方向分化,其可能是通过激活PI3K/AKT信号通路起作用。

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