MicroRNAs and neurogenesis after stroke

MicroRNA 与中风后的神经发生

• 批准号: 8892273
• 负责人: ZHENG GANG ZHANG
• 金额: $ 32.05万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8892273
• 关键词: Ablation; Adult; Affect; Attenuated; Biological Process; Brain; Cell Lineage; Cell Proliferation; Cerebellum; Corpus Callosum; Cytoplasmic Granules; Data; Development; Erinaceidae; Family; Gene Targeting; Generations; Intraventricular Infusion; Knock-out; Lead; Lentivirus Vector; Mediating; MicroRNAs; Molecular; Mus; Mutation; Neurological outcome; Neurons; Nucleotides; Oligodendroglia; Patients; Play; Process; Recovery of Function; Rodent; Role; Sonic Hedgehog Pathway; Stem cells; Stroke; Testing; Tissues; Transfection; Untranslated RNA; adult neurogenesis; brain repair; embryonic stem cell; human DICER1 protein; inhibitor/antagonist; injured; insight; lateral ventricle; member; miRNA expression profiling; nerve stem cell; neurogenesis; novel; overexpression; relating to nervous system; research study; smoothened signaling pathway; subventricular zone

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.

描述（由申请人提供）：微RNA（miRNAs）调节神经祖细胞和少突胶质祖细胞（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祖细胞和少突胶质细胞中的miRNA表达谱。在本申请中，我们提出测试神经和OPCs中的miRNA在介导缺血脑中的成体神经发生和少突神经发生中起关键作用的假设。在具体目标1中，我们将通过Ascl 1谱系细胞（Ascl 1-CreTM/Dicerflox/flox）中的条件性和诱导性Dicer消融来研究神经祖细胞和OPCs中的失活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。在具体目标2中，我们将研究音刺猬（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神经发生。在具体目标3中，我们将通过在中风后的神经祖细胞和OPCs中缺失或过表达miR 17 - 92簇来研究miR 17 - 92簇对缺血脑中的神经和少突胶质细胞祖细胞的生物学功能的影响。这些研究将为miRNAs在调节脑卒中诱导的神经发生和少突胶质细胞发生中的作用提供新的见解，这可能会导致新的治疗方法来增强受损脑中的神经发生和少突胶质细胞发生。