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Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination.

ABSTRACT: Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFR?-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI. While OPC proliferation and density are not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes is largely prevented. This greatly inhibits myelin regeneration, resulting in a 44% reduction in myelinated axons at the lesion epicenter. However, spontaneous locomotor recovery after SCI is not altered by remyelination failure. In controls with functional MYRF, locomotor recovery precedes the onset of most oligodendrocyte myelin regeneration. Collectively, these data demonstrate that MYRF expression in PDGFR?-positive cell derived oligodendrocytes is indispensable for myelin regeneration following contusive SCI but that oligodendrocyte remyelination is not required for spontaneous recovery of stepping.

SUBMITTER: Duncan GJ

PROVIDER: S-EPMC6076268 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination.

Duncan Greg J GJ Manesh Sohrab B SB Hilton Brett J BJ Assinck Peggy P Liu Jie J Moulson Aaron A Plemel Jason R JR Tetzlaff Wolfram W

Nature communications 20180803 1

Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI. While OPC proliferation and density are not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes is largely preven ...[more]

PMID: 30076300

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Project description:It has been reported that oligodendrocyte precursor cells (OPCs) may be used to treat contusive spinal cord injury (SCC), and may alter microRNA (miRNA/miR) expression following SCC in rats. However, the association between miRNA expression and the treatment of rats with SCC with OPC transplantation remain unclear. The present study transplanted OPCs into the spinal cord of rats with SCC and subsequently used the Basso, Beattie and Bresnahan (BBB) score to assess the functional recovery and pain scores. An miRNA assay was performed to detect differentially expressed miRNAs in the spinal cord of SCC rats transplanted with OPCs, compared with SCC rats transplanted with medium. Quantitative polymerase chain reaction was used to verify significantly altered miRNA expression levels. The results demonstrated that OPC transplantation was able to improve motor recovery and relieve mechanical allodynia in rats with SCC. In addition, through a miRNA assay, 45 differentially expressed miRNAs (40 upregulated miRNAs and 5 downregulated miRNAs) were detected in the spinal cord of rats in the OPC group compared with in the Medium group. Differentially expressed miRNAs were identified according to the following criteria: Fold change >2 and P<0.05. Furthermore, quantitative polymerase chain reaction was used to verify the most highly upregulated (miR‑375‑3p and miR‑1‑3p) and downregulated (miR‑363‑3p, miR‑449a‑5p and miR‑3074) spinal cord miRNAs that were identified in the miRNA assay. In addition, a bioinformatics analysis of these miRNAs indicated that miR‑375 and miR‑1 may act primarily to inhibit cell proliferation and apoptosis via transcriptional and translational regulation, whereas miR‑363, miR‑449a and miR‑3074 may act primarily to inhibit cell proliferation and neuronal differentiation through transcriptional regulation. These results suggested that OPC transplantation may promote functional recovery of rats with SCC, which may be associated with the expression of various miRNAs in the spinal cord, including miR‑375‑3p, miR‑1‑3p, miR‑363‑3p, miR‑449a‑5p and miR‑3074.

Dataset Information

Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination.

Publications

Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination.

Similar Datasets

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