β-淀粉样蛋白25～35和人参皂苷Rb1对神经干细胞分化过程中tau蛋白磷酸化水平的影响

Effect of GinsenosideRb1 and beta-amyloid 25-35 on tau phosphorylation in differentiated neural stem cells

背景:通过调节神经干细胞分化过程中的tau蛋白磷酸化水平可提高神经干细胞移植治疗阿尔茨海默病的效果。目的:观察β-淀粉样蛋白25～35和人参皂苷Rb1对神经干细胞分化过程中tau蛋白磷酸化水平的影响。方法:分离、培养新生大鼠海马神经干细胞,诱导第3代神经干细胞分化1周后,分别采用免疫荧光细胞化学和Western-blot检测Tau[pS396]、Tau[pS262]及GSK-3β[pTyr279,216]表达情况。结果与结论:正常神经干细胞分化过程中有Tau[pS396]和Tau[pS262]的表达,β-淀粉样蛋白25～35可以使Tau[pS396]、Tau[pS262]和GSK-3β[pT279/216]表达上调,而人参皂苷Rb1可以逆转β-淀粉样蛋白25～35的作用。提示β-淀粉样蛋白25～35和人参皂苷Rb1通过调节GSK-3β的活性对tau蛋白的磷酸化水平产生调控作用。

BACKGROUND：Currently,neural stem cells（NSCs） transplantation effect on the treatment of Alzheimer＇s disease is improved by adjusting tau protein phosphorylation level during the differentiation of NSCs.OBJECTIVE：To explore the effect of GinsenosideRb1 and beta-amyloid 25-35（Aβ25-35） on tau phosphorylation after NSCs are transformed into neurons.METHODS：NSCs were isolated and cultured from rat hippocampus.NSCs of the third passage were induced towards neurons after one week;the expression of Tau[pS396],Tau[pS262] and GSK-3β[pTyr279,216] were tested by the immunofluorescent cytochemical staining and western-blot.RESULTS AND CONCLUSION：The expression of Tau[pS396],Tau[pS262] and GSK-3β[pTyr279,216] was found in the process of NSCs differentiation.Aβ25-35 could enhance their expression;moreover Ginsenoside Rb1 could reverse the effect of Aβ25-35.The results indicated that there was a certain level of phosphorylation in tau protein during NSCs differentiation.Aβ25-35 and GinsenosideRb1 could regulate the level of tau phosphorylation.The mechanism of its action is by adjusting GSK-3β activity.