MicroRNA-146a Promotes Oligodendrogenesis in Stroke

Abstract

Stroke induces new myelinating oligodendrocytes that are involved in ischemic brain repair. Molecular mechanisms that regulate oligodendrogenesis have not been fully investigated. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression. MiR-146a has been reported to regulate immune response, but the role of miR-146a in oligodendrocyte progenitor cells (OPCs) remains unknown. Adult Wistar rats were subjected to the right middle cerebral artery occlusion (MCAo). In situ hybridization analysis with LNA probes against miR-146a revealed that stroke considerably increased miR-146a density in the corpus callosum and subventricular zone (SVZ) of the lateral ventricle of the ischemic hemisphere. In vitro, over-expression of miR-146a in neural progenitor cells (NPCs) significantly increased their differentiation into O4+ OPCs. Over-expression of miR-146a in primary OPCs increased their expression of myelin proteins, whereas attenuation of endogenous miR-146a suppressed generation of myelin proteins. MiR-146a also inversely regulated its target gene-IRAK1 expression in OPCs. Attenuation of IRAK1 in OPCs substantially increased myelin proteins and decreased OPC apoptosis. Collectively, our data suggest that miR-146a may mediate stroke-induced oligodendrogenesis.

MiR-34a Regulates Axonal Growth of Dorsal Root Ganglia Neurons by Targeting FOXP2 and VAT1 in Postnatal and Adult Mouse

“…Fluorescence in situ hybridization (FISH) in combination with fluorescent immunostaining were performed according to a published protocol [30]. Briefly, the cells were fixed in 4% paraformaldehyde, and then hybridized with a miR-34a LNA (locked nucleic acid) probe, and the probe was detected with peroxidase-conjugated anti-FAM (Roche, Basel, Switzerland) followed by incubation tyramine-signal-amplification (TSA)-Cy3 substrate for 10 min at room temperature.…”

Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application

“…Furthermore, having in mind that microRNA (miRNA)−146a may directly induce OPC differentiation to OLs (Zhang et al, 2017a;Liu et al, 2016b), Tβ4 treatment may prominently stimulate the expression of this mRNA in primary cultured OPCs, thus promoting the proliferation and differentiation of OPCs and OLs (Santra et al, 2014), which may serve as a common remyelination therapeutic mechanism. In addition to increasing miR-146a expression in OPCs, Tβ4 remarkably also increased miR-146a expression in microglia and significantly inhibited secretion of pro-inflammatory mediators (Zhou et al, 2015), all of which may promote remyelination (Crockford, 2007).…”

Overview of Advances in the Pathophysiology and Treatment of Stroke: A New Plan for Stroke Treatment

“…Targeting other cells such as oligodendrocytes that may help better healing of ischemic region is also a useful treatment. MicroRNA 146a promotes oligodendrocytes in the ischemic region [51].…”