MicroRNA-219 Inhibits Proliferation and Induces Differentiation of Oligodendrocyte Precursor Cells after Contusion Spinal Cord Injury in Rats

Fang Li,Yan-Yan Yang,Xiao-Xie Liu,Hua-Yi Xing,Mou-Wang Zhou,Yao Lu,Nan Liu

doi:10.1155/2019/9610687

Abstract

MicroRNA-219 (miR-219) regulates the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) during central nervous system (CNS) development. OPCs only differentiate into oligodendrocytes (OLs) in the healthy CNS, but can generate astrocytes (As) after injury. We hypothesized that miR-219 may modulate OPC proliferation and differentiation in a cervical C5 contusion spinal cord injury (SCI) model. After injury, we observed a decrease in the miR-219 level and quantity of OLs and an increase in the number of OPCs and As. Silencing of miR-219 by its antagomir in vivo produced similar results, but of greater magnitude. Overexpression of miR-219 by its agomir in vivo increased the number of OLs and suppressed generation of OPCs and As. Luxol fast blue staining confirmed that SCI caused demyelination and that the extent of demyelination was attenuated by miR-219 overexpression, but aggravated by miR-219 reduction. Monocarboxylate transporter 1 (MCT-1) may be implicated in the regulation of OPC proliferation and differentiation mediated by miR-219 following contusion SCI. Collectively, our data suggest that miR-219 may mediate SCI-induced OPC proliferation and differentiation, and MCT-1 may participate in this process as a target of miR-219.

Highlights

Spinal cord injury (SCI) is a common and serious injury of the central nervous system (CNS) typically resulting in sustained sensorimotor dysfunction and can severely affect patients’ quality of life [1]
The Quantitative Real-Time PCR (qRT-PCR) results demonstrated that miR-219 expression was increased over the time course in the agomir-219 group and was downregulated in the antagomir-219 group
Several studies have reported that expression of miR-219 is decreased after CNS injury, but how the expression level of miR-219 is affected by SCI, in particular at the acute and subacute SCI phases, remains unclear [40,41,42]

Summary

Introduction

Spinal cord injury (SCI) is a common and serious injury of the central nervous system (CNS) typically resulting in sustained sensorimotor dysfunction and can severely affect patients’ quality of life [1]. SCI involves both primary neural injury and secondary tissue damage. Primary injury is caused by initial mechanical change. Secondary damage is induced by vascular and biochemical changes and leads to oligodendrocyte death and axon demyelination, which may leave axons vulnerable to degeneration. Targeting remyelination of axons therapeutically to promote functional benefits is considered a potential treatment strategy after SCI [1,2,3]. Mature oligodendrocytes (OLs) are the sole myelinating cells of the CNS. OLs support axons and maintain neurological function. The death of OLs after SCI leads to demyelination and thereby exacerbates neurological deficits.

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Results

Conclusion