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首页> 外文期刊>The European Journal of Neuroscience >Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation
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Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation

机译:苯妥英钠增强心室下区表皮生长因子受体和成纤维细胞生长因子受体的磷酸化,并促进神经前体细胞的增殖和少突胶质细胞的分化

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Phenytoin is a widely used antiepileptic drug that induces cell proliferation in several tissues, such as heart, bone, skin, oral mucosa and neural precursors. Some of these effects are mediated via fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR). These receptors are strongly expressed in the adult ventricular-subventricular zone (V-SVZ), the main neurogenic niche in the adult brain. The aim of this study was to determine the cell lineage and cell fate of V-SVZ neural progenitors expanded by phenytoin, as well as the effects of this drug on EGFR/FGFR phosphorylation. Male BALB/C mice received 10 mg/kg phenytoin by oral cannula for 30 days. We analysed the proliferation of V-SVZ neural progenitors by immunohistochemistry and western blot. Our findings indicate that phenytoin enhanced twofold the phosphorylation of EGFR and FGFR in the V-SVZ, increased the number of bromodeoxyuridine (BrdU)+/Sox2+ and BrdU+/doublecortin+ cells in the V-SVZ, and expanded the population of Olig2-expressing cells around the lateral ventricles. After phenytoin removal, a large number of BrdU+/ Receptor interacting protein (RIP)+ cells were observed in the olfactory bulb. In conclusion, phenytoin enhanced the phosphorylation of FGFR and EGFR, and promoted the expression of neural precursor markers in the V-SVZ. In parallel, the number of oligodendrocytes increased significantly after phenytoin removal.
机译:苯妥英钠是一种广泛使用的抗癫痫药,可在心脏,骨骼,皮肤,口腔粘膜和神经前体等多种组织中诱导细胞增殖。其中一些作用是通过成纤维细胞生长因子受体(FGFR)和表皮生长因子受体(EGFR)介导的。这些受体在成人脑室下区域(V-SVZ)(成人脑中主要的神经源利基)中强烈表达。这项研究的目的是确定苯妥英钠扩增的V-SVZ神经祖细胞的细胞谱系和细胞命运,以及该药物对EGFR / FGFR磷酸化的影响。雄性BALB / C小鼠经口腔插管接受10 mg / kg苯妥英钠治疗30天。我们通过免疫组织化学和免疫印迹分析了V-SVZ神经祖细胞的增殖。我们的发现表明,苯妥英钠可将V-SVZ中的EGFR和FGFR磷酸化提高两倍,增加V-SVZ中溴脱氧尿苷(BrdU)+ / Sox2 +和BrdU + / doublecortin +细胞的数量,并扩大表达Olig2的细胞的数量侧脑室周围。苯妥英钠去除后,在嗅球中观察到大量的BrdU + /受体相互作用蛋白(RIP)+细胞。总之,苯妥英钠可增强FGFR和EGFR的磷酸化,并促进V-SVZ中神经前体标志物的表达。同时,苯妥英钠去除后少突胶质细胞的数量显着增加。

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