Modulation of bone morphogenic protein signalling alters numbers of astrocytes and oligodendroglia in the subventricular zone during cuprizone-induced demyelination
Modulation of bone morphogenic protein signalling alters numbers of astrocytes and oligodendroglia in the subventricular zone during cuprizone-induced demyelination
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DOI：
10.1111/j.1471-4159.2010.06660.x
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发表时间：
2010-10-01
影响因子：
4.7
通讯作者：
Kilpatrick, Trevor J.
中科院分区：
文献类型：
--
作者：
Cate, Holly S.;Sabo, Jennifer K.;Kilpatrick, Trevor J.
成人心室下区（SVZ）是替代脱髓鞘过程中丢失的神经细胞的前体细胞的潜在来源。为了更好地了解在这种情况下调节神经前体细胞反应性的分子事件，我们对铜酮诱导脱髓鞘过程中SVZ内表达的基因进行了微阵列和定量PCR分析。我们发现编码骨形态发生蛋白4 （BMP4）及其受体的基因上调。免疫组织化学证实在脱髓鞘过程中BMP4蛋白水平升高，磷酸化的SMAD 1/5/8 （BMP4信号传导的关键成分）也增加。体外分析显示，从脱髓鞘动物分离的神经前体细胞，以及用BMP4处理的神经前体细胞，产生更多的星形胶质细胞。同样，在脱髓鞘过程中，SVZ内的星形胶质细胞数量增加。在铜酮诱导的脱髓鞘过程中，脑室内输注Noggin（一种内源性BMP4拮抗剂）可降低SVZ的pSMAD1/5/8，减少星形胶质细胞数量，增加少突胶质细胞数量。我们的研究结果表明，SVZ神经前体细胞的谱系承诺在脱髓鞘过程中发生改变，BMP信号在这一过程中起作用。
P>The adult subventricular zone (SVZ) is a potential source of precursor cells to replace neural cells lost during demyelination. To better understand the molecular events that regulate neural precursor cell responsiveness in this context we undertook a microarray and quantitative PCR based analysis of genes expressed within the SVZ during cuprizone-induced demyelination. We identified an up-regulation of the genes encoding bone morphogenic protein 4 (BMP4) and its receptors. Immunohistochemistry confirmed an increase in BMP4 protein levels and also showed an increase in phosphorylated SMAD 1/5/8, a key component of BMP4 signalling, during demyelination. In vitro analysis revealed that neural precursor cells isolated from demyelinated animals, as well as those treated with BMP4, produce more astrocytes. Similarly, there were increased numbers of astrocytes in vivo within the SVZ during demyelination. Intraventricular infusion of Noggin, an endogenous antagonist of BMP4, during cuprizone-induced demyelination reduced pSMAD1/5/8, decreased astrocyte numbers and increased oligodendrocyte numbers in the SVZ. Our results suggest that lineage commitment of SVZ neural precursor cells is altered during demyelination and that BMP signalling plays a role in this process.