Effects of miR-219/miR-338 on microglia and astrocyte behaviors and astrocyte-oligodendrocyte precursor cell interactions

Abstract

MiR-219 and miR-338 (miR-219/miR-338) are oligodendrocyte-specific microRNAs. The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes, which may enhance axonal remyelination after nerve injuries in the central nervous system (CNS). As such, the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation, maturation and myelination could be a promising approach for nerve repair. However, nerve injuries in the CNS also involve other cell types, such as microglia and astrocytes. Herein, we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo. We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation. In addition, we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro. Collectively, our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries. All experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC), Nanyang Technological University (approval No. A0309 and A0333) on April 27, 2016 and October 8, 2016.