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）：微小RNA（miRNA）调节神经祖细胞和少突胶质细胞祖细胞（OPC）的生物学功能。我们的初步数据表明，中风显着改变了成体神经祖细胞和少突胶质细胞中的 miRNA 表达谱。在此应用中，我们建议测试以下假设：神经和 OPC 中的 miRNA 在介导缺血性大脑中的成体神经发生和少突胶质细胞发生中发挥关键作用。在具体目标 1 中，我们将通过 Ascl1 谱系细胞 (Ascl1-CreTM/Dicerflox/flox) 中条件性和诱导性 Dicer 消融来研究神经祖细胞和 OPC 中失活的 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胶质细胞发生。在具体目标 3 中，我们将通过中风后神经祖细胞和 OPC 中 miR17-92 簇的缺失或过表达来研究 miR17-92 簇对缺血脑中神经祖细胞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发生中提供新的见解，这可能会带来新的疗法来放大受损大脑中的神经发生和少突胶质细胞发生。