MicroRNAs and neurogenesis after stroke

描述（由申请人提供）：MicroRNAs （miRNAs）调节神经祖细胞和少突胶质细胞祖细胞（OPCs）的生物学功能。我们的初步数据显示，中风显著改变了成人神经祖细胞和少突胶质细胞中miRNA的表达谱。在这项应用中，我们提出验证神经和OPCs中的mirna在缺血性脑中介导成人神经发生和少突胶质发生中起关键作用的假设。在Specific Aim 1中，我们将通过Ascl1谱系细胞（Ascl1- cretm /Dicerflox/flox）的条件和诱导Dicer消融，研究神经祖细胞和OPCs中失活性miRNA过程对中风诱导的神经发生和少突胶质细胞发生的影响。在Specific Aim 2中，我们将研究sonic hedgehog （Shh）信号通路是否与miR-17-92簇相互作用以增加神经发生和少突胶质发生。在Specific Aim 3中，我们将通过在脑卒中后神经祖细胞和OPCs中缺失或过表达miR17-92簇来研究miR17-92簇对缺血性脑神经和少突胶质细胞祖细胞生物学功能的影响。这些研究将为mirna在调节中风诱导的神经发生和少突胶质细胞形成方面提供新的见解，这可能会导致新的治疗方法来扩大损伤脑中的神经发生和少突胶质细胞形成。

DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) regulate biological function of neural progenitor cells and oligodendrocyte progenitor cells (OPCs). Our preliminary data show that stroke substantially changed miRNA expression profiles in adult neural progenitor cells and oligodendrocytes. In this application, we propose to test the hypothesis that miRNAs in neural and OPCs play a pivotal role in mediating adult neurogenesis and oligodendrogenesis in the ischemic brain. In Specific Aim 1, we will investigate the effect of inactive miRNA processes in neural progenitor cells and OPCs on stroke-induced neurogenesis and oligodendrogenesis by conditional and inducible Dicer ablation in Ascl1 lineage cells (Ascl1-CreTM/Dicerflox/flox). In Specific Aim 2, we will investigate whether the sonic hedgehog (Shh) signaling pathway interacts with the miR-17-92 cluster to increase neurogenesis and oligodendrogenesis. In Specific Aim 3, we will investigate the effect of the miR17-92 cluster on biological function of neural and oligodendrocyte progenitor cells in the ischemic brain by deletion or overexpression of the miR17-92 cluster in neural progenitor cells and OPCs after stroke. These studies will provide novel insights into miRNAs in regulating stroke-induced neurogenesis and oligodendrogenesis, which could potentially lead to new therapies to amplify neurogenesis and oligodendrogenesis in injured brain.