NG2 Glia Generate New Oligodendrocytes But Few Astrocytes in a Murine Experimental Autoimmune Encephalomyelitis Model of Demyelinating Disease

Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 12/2010; 30(48):16383-90. DOI: 10.1523/JNEUROSCI.3411-10.2010
Source: PubMed


The adult mammalian brain and spinal cord contain glial precursors that express platelet-derived growth factor receptor α subunit (PDGFRA) and the NG2 proteoglycan. These "NG2 cells" descend from oligodendrocyte precursors in the perinatal CNS and continue to generate myelinating oligodendrocytes in the gray and white matter of the postnatal brain. It has been proposed that NG2 cells can also generate reactive astrocytes at sites of CNS injury or demyelination. To test this we examined the fates of PDGFRA/NG2 cells in the mouse spinal cord during experimental autoimmune encephalomyelitis (EAE)--a demyelinating condition that models some aspects of multiple sclerosis in humans. We administered tamoxifen to Pdgfra-CreER(T2):Rosa26R-YFP mice to induce yellow fluorescent protein (YFP) expression in PDGFRA/NG2 cells and their differentiated progeny. We subsequently induced EAE and observed a large (>4-fold) increase in the local density of YFP(+) cells, >90% of which were oligodendrocyte lineage cells. Many of these became CC1-positive, NG2-negative differentiated oligodendrocytes that expressed myelin markers CNP and Tmem10/Opalin. PDGFRA/NG2 cells generated very few GFAP(+)-reactive astrocytes (1-2% of all YFP(+) cells) or NeuN(+) neurons (<0.02%). Thus, PDGFRA/NG2 cells act predominantly as a reservoir of new oligodendrocytes in the demyelinated spinal cord.

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Available from: Richa B Tripathi,
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    • "Experimental studies demonstrate the default response to immune-mediated demyelination in the CNS is rapid remyelination by oligodendrocytes derived from an endogenous pool of mitotic CSPG4 + (also known as NG2 + ) oligodendrocyte progenitor cells (OPCs; Tripathi et al., 2010). However, in multiple sclerosis this repair mechanism frequently fails resulting in chronically demyelinated plaques of gliotic scar tissue (Franklin and Ffrench- Constant, 2008). "
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    • "The adult mammalian CNS contains glial precursor cells that express the NG2 proteoglycan, which are known to descend from OPCs in the perinatal CNS. NG2+ cells generate myelinating oligodendrocytes and a limited number of astrocytes to the postnatal brain in EAE [203]. Interestingly, NG2+ cells and mature oligodendrocytes are decreased within areas of subpial cortical demyelination in chronic but not early stage MS [204]. "
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    • "Lesions are interspersed throughout the CNS and do not necessarily occur in the same anatomical regions [7]. Within the lesion myelin loss and new myelin formation occur in a dynamic process and can vary significantly between lesions [8], [9]. Inter-animal variability adds another level of complexity as clinical deficits and disease pathology can vary in timing and severity among a cohort. "
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