Sema4C Expression in Neural Stem/Progenitor Cells and in Adult Neurogenesis Induced by Cerebral Ischemia
Sema4C Expression in Neural Stem/Progenitor Cells and in Adult Neurogenesis Induced by Cerebral Ischemia
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Sema4C 在神经干/祖细胞和脑缺血诱导的成人神经发生中的表达
DOI：
10.1007/s12031-009-9177-8
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发表时间：
2009-09-01
影响因子：
3.1
通讯作者：
Fan, Ming
中科院分区：
文献类型：
--
作者：
Wu, Haitao;Fan, Jundie;Fan, Ming
Sema 4C是一种跨膜蛋白，属于脑信号蛋白家族的轴突导向分子。以往的研究表明Sema 4C可以与突触后蛋白PSD 95等相互作用，但Sema 4C在神经发生中的表达及其作用尚不清楚。本研究中，整体原位杂交结果显示，Sema 4C在E11.5胚胎脑的侧脑室、纹状体、中脑壁和脑桥/中脑连接区有丰富的表达。从E13.5胚胎大鼠中脑获得的神经干/祖细胞（NSP）也为Sema 4C免疫反应性阳性。Sema 4C表达在NSP分化诱导过程中显著下调。为了证实Sema 4C参与神经发生，我们采用大鼠全脑缺血模型，在体内进行成体神经发生。通过在室下区和齿状回内用溴脱氧尿苷（BrdU）标记持续至少2周来监测稳健的增殖性NSP。免疫组化和Western blot分析显示，脑缺血再灌注损伤后Sema 4C表达在神经发生过程中显著上调。免疫组化和体视学计数分析表明，在缺血损伤后的特定阶段，高比例的BrdU阳性增殖细胞是Nestin阳性的NSPs，Sema 4C在这些增殖细胞中高度表达。这些观察结果提供的证据支持Sema 4C在体内和体外神经发生过程中的假定作用。
Sema4C is a transmembrane protein that belongs to axon guidance molecules of semaphorin family. Previous reports have shown that Sema4C could interact with postsynaptic protein PSD95, etc, but the expression and the role of Sema4C in neurogenesis remains unknown. In this study, whole-mount in situ hybridization result showed that Sema4C was expressed abundantly in the areas of lateral ventricle, the striatum, the wall of midbrain, and the pons/midbrain junction of E11.5 embryos brain. Neural stem/progenitor cells (NSPs) obtained from E13.5 embryonic rat midbrain are also positive for Sema4C immunoreactivity. Sema4C expression was dramatically downregulated during induction of NSP differentiation. In order to confirm the involvement of Sema4C in neurogenesis, we used the rat global cerebral ischemia model to make adult neurogenesis in vivo. The robust proliferative NSPs were monitored by labeling with bromodeoxyuridine (BrdU) within the subventricular zone and dentate gyrus that continues for at least 2 weeks. Immunohistochemistry and Western blot analysis showed that Sema4C expression was dramatically upregulated during neurogenesis after cerebral ischemia-perfusion injury. Double immunostaining and stereologic counting analysis indicated that a high proportion of BrdU-positive proliferative cells were Nestin-positive NSPs, and also, Sema4C was highly expressed in these proliferative populations at specific stages after ischemic injury. These observations provide the evidence to support a putative role of Sema4C during neurogenesis both in vivo and in vitro.