MicroRNAs and neurogenesis after stroke

描述(申请人提供)：microRNAs(MiRNAs)调节神经前体细胞和少突胶质前体细胞(OPC)的生物学功能。我们的初步数据显示，中风显著改变了成年神经前体细胞和少突胶质细胞的miRNA表达谱。在这一应用中，我们建议检验一种假设，即神经和OPC中的miRNAs在介导缺血脑中的成年神经发生和少突胶质发生中发挥关键作用。在具体目标1中，我们将通过对Ascl1系细胞(Ascl1-CreTM/Dicerflx/FLOX)进行条件性和可诱导性DICER消融，研究神经前体细胞和OPC中不活跃的miRNA过程在卒中诱导的神经发生和少突胶质细胞形成中的作用。在特定的目标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形成。在具体目标3中，我们将通过在卒中后神经前体细胞和OPC中缺失或过表达miR17-92簇来研究miR17-92簇对缺血脑内神经和少突胶质前体细胞生物学功能的影响。这些研究将为miRNAs在调节卒中诱导的神经发生和少突胶质细胞发生中提供新的见解，这可能导致扩大受损脑内神经新生和少突胶质细胞形成的新疗法。

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.