MicroRNAs participate in the murine oligodendroglial response to perinatal hypoxia-ischemia

BACKGROUND: Hypoxic-ischemic injury (HI) to preterm brain results in white matter loss. The endogenous oligodendroglial response to perinatal HI is characterized by increased oligodendroglial progenitor cells (OPCs). MicroRNAs (miRs) are important post-transcriptional regulators of gene expression, and a few miRs have been shown to regulate differentiation of OPCs into mature oligodendroglia (OLs). We tested the hypothesis that microRNAs play a role in the increase in OPCs in response to perinatal HI. METHODS: We inducibly deleted the miR-processing enzyme Dicer in OPCs using a tamoxifen-inducible NG2CreER(T2) transgene in Dicer(fl/fl) mice. After HI, mice were analyzed for OPC differentiation using immunofluorescence and for white matter formation by Luxol fast blue (LFB) staining. Functional recovery from injury was investigated using digital gait analysis. We also tested whether HI changed miRs known to regulate OPC differentiation using quantitative RT-PCR. RESULTS: Perinatal HI induced significant increases in miR-138 and miR-338, two microRNAs known to regulate OPC differentiation. Knockdown of Dicer increased myelin basic protein (MBP) and LFB staining within corpus callosum after HI. In addition, there was significant improvement in motor function 14 and 24 days post lesion. CONCLUSION: Changes in specific mature miRs expressed in OPCs following HI may contribute to white matter injury.