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Open Access Highly Accessed Research

Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord

Karolina Kucharova1*, Yunchao Chang12, Andrej Boor3, Voon Wee Yong4 and William B Stallcup1

Author Affiliations

1 Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA

2 St Jude Children's Research Hospital, Memphis, TN 38105, USA

3 Department of Pathology, P.J. Safárik University, Faculty of Medicine, Kosice 04001, Slovak Republic

4 Departments of Oncology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, T2N 4N1, Canada

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Journal of Neuroinflammation 2011, 8:158  doi:10.1186/1742-2094-8-158

Published: 13 November 2011

Abstract

Background

Multiple sclerosis (MS) is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs) are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination.

Methods

Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR.

Results

The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype.

Conclusions

Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result of these NG2-dependent changes, the course of demyelination and remyelination in NG2 null mice differs from that seen in wild type mice, with both myelin damage and repair being reduced in the NG2 null mouse. These studies identify NG2 as an important factor in regulating myelin processing, suggesting that therapeutic targeting of the proteoglycan might offer a means of manipulating cell behavior in demyelinating diseases.

Keywords:
Inflammation; myelin repair; NG2 ablation; oligodendrocyte progenitors; pericytes; macrophages