The Notch pathway mediates expansion of a progenitor pool and neuronal differentiation in adult neural progenitor cells after stroke.
The Notch pathway mediates expansion of a progenitor pool and neuronal differentiation in adult neural progenitor cells after stroke.
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DOI：
10.1016/j.neuroscience.2008.10.064
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发表时间：
2009-02-18
期刊：
影响因子：
3.3
通讯作者：
Zhang ZG
中科院分区：
文献类型：
--
作者：
Wang L;Chopp M;Zhang RL;Zhang L;Letourneau Y;Feng YF;Jiang A;Morris DC;Zhang ZG
中风增加神经发生的分子机制尚未完全研究。本实验采用成年大鼠局灶性脑缺血后室管膜下区（SVZ）分离的神经前体细胞，研究Notch信号通路在脑缺血后神经前体细胞增殖和分化中的作用。在神经前体细胞增殖过程中，缺血神经前体细胞表现出Notch、Notch胞内结构域（NICD）和Hes1水平的显著增加，这与增殖细胞的显著增加相关。通过针对Notch的siRNA或γ分泌酶抑制剂阻断Notch通路显著降低了Notch、NICD和Hes1的表达以及由中风诱导的细胞增殖。在神经前体细胞分化过程中，缺血神经前体细胞Notch和Hes1表达下调，与神经元数量显著增加相一致。用γ分泌酶抑制剂抑制Notch途径进一步显著增加神经元，但不改变缺血神经祖细胞中的星形胶质细胞群。这些数据表明，Notch信号通路介导成年SVZ神经祖细胞增殖和分化后中风。
Molecular mechanisms by which stroke increases neurogenesis have not been fully investigated. Using neural progenitor cells isolated from the subventricular zone (SVZ) of the adult rat subjected to focal cerebral ischemia, we investigated the Notch pathway in regulating proliferation and differentiation of adult neural progenitor cells after stroke. During proliferation of neural progenitor cells, ischemic neural progenitor cells exhibited substantially increased levels of Notch, Notch intracellular domain (NICD), and Hes1, which was associated with a significant increase of proliferating cells. Blockage of the Notch pathway by siRNA against Notch or a γ secretase inhibitor significantly reduced Notch, NICD and Hes1 expression and cell proliferation induced by stroke. During differentiation of neural progenitor cells, Notch and Hes1 expression was downregulated in ischemic neural progenitor cells, which was coincident with a significant increase of neuronal population. Inhibition of the Notch pathway with a γ secretase inhibitor further substantially increased neurons, but did not alter astrocyte population in ischemic neural progenitor cells. These data suggest that the Notch signaling pathway mediates adult SVZ neural progenitor cell proliferation and differentiation after stroke.
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影响因子：
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