N-cadherin mediates nitric oxide-induced neurogenesis in young and retired breeder neurospheres
N-cadherin mediates nitric oxide-induced neurogenesis in young and retired breeder neurospheres
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DOI：
10.1016/j.neuroscience.2006.02.064
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Chopp, M.
中科院分区：
文献类型：
--
作者：
Chen, J.;Zacharek, A.;Chopp, M.
神经再生可能有助于神经损伤后的功能恢复。一氧化氮供体如DETANONOate可促进卒中后的功能恢复。然而，功能改善的机制尚未确定。因此，我们研究了α-NONOate对来自年轻和退休的饲养大鼠脑的脑室下区的神经祖细胞/干细胞神经球的影响。从正常年轻成年雄性Wistar大鼠（2-3月龄）和退休的育种大鼠（14月龄）中分离室下区细胞，用或不用α-NONOate处理。室管膜下区神经球的形成，增殖，端粒酶活性，和Neurogenin I mRNA的表达显着降低和胶质细胞酸性蛋白的表达显着增加，在室管膜下区神经球从退休的饲养大鼠与年轻的大鼠相比。用α-NONOate处理神经球显著降低了神经球形成和端粒酶活性，促进了神经元分化和轴突生长，同时增加了年轻和年老神经球中的N-钙粘蛋白和β-连环蛋白mRNA表达。NONOate选择性地增加神经生成素1和减少胶质细胞酸性蛋白mRNA的表达在退休的饲养员神经球。N-cadherin显著增加了年轻和老年神经球中Neurogenin I mRNA的表达。抗N-钙粘蛋白逆转了α-NONOate诱导的神经球粘附、神经元分化、神经突生长和β-连环蛋白mRNA表达。我们的数据表明，年龄对室管膜下区神经球的特征有很强的影响;年轻大鼠的神经球比老年神经球显示出更高的形成、增殖和端粒酶活性。相比之下，老年神经球表现出显着增加的胶质细胞分化比年轻的神经球。NONOate促进年轻和老年神经球中的神经元分化和神经突生长。与来自年轻和老年动物的神经球的α-NONOate调节以及神经球的年龄依赖性效应相关的分子机制似乎受到N-钙粘蛋白和β-连环蛋白基因表达的控制，其随后调节年轻和老年神经祖细胞中的神经元分化因子Neurogenin表达。(c)2006由Elsevier Ltd代表IBRO出版。
Neurogenesis may contribute to functional recovery after neural injury. Nitric oxide donors such as DETANONOate promote functional recovery after stroke. However, the mechanisms underlying functional improvement have not been ascertained. We therefore investigated the effects of DETA-NONOate on neural progenitor/stem cell neurospheres derived from the subventricular zone from young and retired breeder rat brain. Subventricular zone cells were dissociated from normal young adult male Wistar rats (2-3 months old) and retired breeder rats (14 months old), treated with or without DETA-NONOate. Subventricular zone neurosphere formation, proliferation, telomerase activity, and Neurogenin I mRNA expression were significantly decreased and glial fibrillary acidic protein expression was significantly increased in subventricular zone neurospheres from retired breeder rats compared with young rats. Treatment of neurospheres with DETA-NONOate significantly decreased neurosphere formation and telomerase activity, and promoted neuronal differentiation and neurite outgrowth concomitantly with increased N-cadherin and beta-catenin mRNA expression in both young and old neurospheres. DETA-NONOate selectively increased Neurogenin 1 and decreased glial fibrillary acidic protein mRNA expression in retired breeder neurospheres. N-cadherin significantly increased Neurogenin I mRNA expression in young and old neurospheres. Anti-N-cadherin reversed DETA-NONOate-induced neurosphere adhesion, neuronal differentiation, neurite outgrowth, and beta-catenin mRNA expression. Our data indicate that age has a potent effect on the characteristics of subventricular zone neurospheres; neurospheres from young rats show significantly higher formation, proliferation and telomerase activity than older neurospheres. In contrast, older neurospheres exhibit significantly increased glial differentiation than young neurospheres. DETA-NONOate promotes neuronal differentiation and neurite outgrowth in both young and older neurospheres. The molecular mechanisms associated with the DETA-NONOate modulation of neurospheres from young and older animals as well age dependent effects of neurospheres appear to be controlled by N-cadherin and beta-catenin gene expression, which subsequently regulates the neuronal differentiating factor Neurogenin expression in both young and old neural progenitor cells. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.