Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke
Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke
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DOI：
10.1016/j.neures.2013.01.006
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Tanigaki, Kenji
中科院分区：
文献类型：
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作者：
Marumo, Takeshi;Takagi, Yasushi;Tanigaki, Kenji
已知用DAPT（一种Notch激活酶γ-分泌酶的抑制剂）治疗可减少对缺血性脑的损伤。然而，支持这种治疗效果的分子机制尚未完全了解。在这里，我们证明了Notch/RBP-J信号转导在NG 2（+）胶质祖细胞和反应性星形胶质细胞如GFAP（+）细胞、Nestin（+）细胞和RC 2（+）细胞中被激活，使用Notch/RBP-J信号转导报告小鼠。3-DAPT处理10天减少了反应性星形胶质细胞的数量，但不减少NG 2（+）胶质祖细胞的数量。BrdU标记实验表明，这种减少是由于反应性星形胶质细胞增殖减少。DAPT抑制Olig 2的核转位，Olig 2是反应性星形胶质细胞增殖和分化所必需的。这些结果表明，Notch信号可能通过调节Olig 2的核质易位促进反应性星形胶质细胞的增殖和分化。(C)2013 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Treatment with DAPT, an inhibitor of the Notch-activating enzyme, gamma-secretase is known to reduce damage to ischemic brain. However, the molecular mechanisms supporting this therapeutic effect are not fully understood. Here we demonstrated that Notch/RBP-J signaling is activated in NG2(+) glial progenitors and reactive astrocytes such as GFAP(+) cells, Nestin(+) cells and RC2(+) cells, using Notch/RBP-J signaling reporter mice. 3-day DAPT treatment reduced the number of reactive astrocytes but not NG2(+) glial progenitors. BrdU labeling experiments have shown that this reduction was due to decreased proliferation of reactive astrocytes. DAPT inhibited nuclear-translocation of Olig2, which is indispensable for proliferation and differentiation of reactive astrocytes. These findings suggest that Notch signaling might promote proliferation and differentiation of reactive astrocytes through the regulation of nucleo-cytoplasmic translocation of Olig2. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.