中国病理生理杂志2014，Vol.30Issue(3)：467-472,6.DOI:10.3969/j.issn.1000-4718.2014.03.015
阿尔茨海默病小鼠模型中骨髓间充质干细胞的神经分化
Neural differentiation of bone marrow mesenchymal stem cells from an Alzheimer disease mouse model
摘要
Abstract
AIM: To estimate the neural differentiation efficiency of bone marrow mesenchymal stem cells (MSCs) derived from amyloid precursor protein (APP) transgenic mice and to investigate the correlation with Notch 1 sig-naling and the autophagy activity during the differentiation .METHODS:The MSCs were divided into APP group (MSCs from APP transgenic mice) and WT group (MSCs from wild-type mice).MSCs were treated with β-mercaptoethanol as an inducer for differentiating into neurons .The levels of Aβ40 and Aβ42 were measured using enzyme-linked immunosorbent assay kits.The expression of neural cell-specific markers, neuron-specific enolase (NSE) and microtubule-associated pro-tein 2 (MAP-2), was measured by immunocytochemistry and Western blotting .The expression levels of Notch1, Notch in-tracellular domain (NICD), Hes5, LC3 and p62 (a selective substrate of autophagy ) were also detected by Western blot-ting.RESULTS:The neural differentiation capacity and the Aβexpression level of the MSCs in APP group were higher than those in WT group, and stronger inhibition of Notch1 signaling pathway in the MSCs from APP group was observed . However, the process of autophagy, which is essential for the survival and function of the neural cells , was impaired in the neural differentiated counterpart of the MSCs in APP group .CONCLUSION:Over-expression of APP might contribute to the high neural differentiation capacity of MSCs by inhibiting Notch 1 signaling pathway in vitro.However, autophagy is im-paired in the differentiated MSCs from APP transgenic mice.关键词
淀粉样前体蛋白/骨髓间充质干细胞/Notch1蛋白/神经元/自噬Key words
Amyloid precursor protein/Bone marrow mesenchymal stem cells/Notch1 protein/Neurons/Au-tophagy分类
医药卫生引用本文复制引用
高慧丽,张广宇,段冉冉,李燕飞,王笑寒,彭涛,关文娟,贾延劼..阿尔茨海默病小鼠模型中骨髓间充质干细胞的神经分化[J].中国病理生理杂志,2014,30(3):467-472,6.基金项目
国家重点基础研究发展计划(973计划)(No.2011CB707501) （973计划）
广州市科技计划项目重大专项(No.11BppZXaa2070006) （No.11BppZXaa2070006）
国家自然科学基金资助项目(No.81371442) （No.81371442）
