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.
Neurogenesis and oligodendrogenesis are associated with functional recovery after stroke. Molecular mechanisms underlying generation of new neurons and oligodendrocytes in ischemic brain have not been fully understood. Our preliminary data suggest that MicroRNAs (miRNAs), short noncoding RNA molecules, could be essential components in mediating stroke-induced neurogenesis and oligodendrogenesis. In this application, we propose three experiments to investigate the role of miRNAs in regulating adult neurogenesis and oligodendrogenesis in the ischemic brain. We will first delete Dicer to inactive miRNA processes in neural progenitor cells and oligodendrocyte progenitor cells (OPCs) after stroke. We will then examine a linkage between the sonic hedgehog (Shh) signaling pathway and miR17-92 expression in mediating neurogenesis and oligodendrogenesis. Finally, we will ablate or overexpress the miR17-92 cluster in neural progenitor cells and OPCs. 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.
|Xin, Hongqi; Katakowski, Mark; Wang, Fengjie et al. (2017) MicroRNA cluster miR-17-92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats. Stroke 48:747-753|
|Xin, Hongqi; Wang, Fengjie; Li, Yanfeng et al. (2017) Secondary Release of Exosomes From Astrocytes Contributes to the Increase in Neural Plasticity and Improvement of Functional Recovery After Stroke in Rats Treated With Exosomes Harvested From MicroRNA 133b-Overexpressing Multipotent Mesenchymal Stromal Ce Cell Transplant 26:243-257|
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|Zhang, Yi; Chopp, Michael; Liu, Xian Shuang et al. (2017) Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons. Mol Neurobiol 54:2659-2673|
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|Liu, Xian Shuang; Fan, Baoyan; Szalad, Alexandra et al. (2017) MicroRNA-146a Mimics Reduce the Peripheral Neuropathy in Type 2 Diabetic Mice. Diabetes 66:3111-3121|
|Jiang, Quan; Zhang, Li; Ding, Guangliang et al. (2017) Impairment of the glymphatic system after diabetes. J Cereb Blood Flow Metab 37:1326-1337|
|Liu, Xian Shuang; Fan, Bao Yan; Pan, Wan Long et al. (2017) Identification of miRNomes associated with adult neurogenesis after stroke using Argonaute 2-based RNA sequencing. RNA Biol 14:488-499|
|Jia, Longfei; Wang, Lei; Chopp, Michael et al. (2017) MiR-29c/PRKCI Regulates Axonal Growth of Dorsal Root Ganglia Neurons Under Hyperglycemia. Mol Neurobiol :|
|Zhang, Zheng Gang; Chopp, Michael (2016) Exosomes in stroke pathogenesis and therapy. J Clin Invest 126:1190-7|
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