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

Abstract

The adult mammalian brain and spinal cord contain glial precursors that express platelet-derived growth factor receptor ␣ 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

How to make an oligodendrocyte

“…Comprising ∼5% of all cells in the adult mouse brain and ∼3% of cells in the adult human brain (Roy et al, 1999;Scolding, 1998;Scolding et al, 1999), these parenchymal OPCs appear to provide the substrate by which normal myelin turnover is maintained (Franklin and ffrench-Constant, 2008). Importantly, although resident adult OPCs have been described as giving rise either predominantly or solely to oligodendrocytes (Kang et al, 2010;Rivers et al, 2008;Tripathi et al, 2010) or to both astrocytes and oligodendrocytes (Nishiyama et al, 2009) in vivo, they have also been reported to generate pyriform projection neurons in adult rodents, even in the absence of injury or exogenous manipulation (Guo et al, 2010;Rivers et al, 2008). Moreover, once removed from the brain, adult OPCs can also produce functional neurons of a variety of phenotypes, both in vitro and upon re-introduction into developing brains (Belachew et al, 2003;Nunes et al, 2003).…”

Cell Therapy for Multiple Sclerosis

“…Tissue OPCs expressing NG2 and platelet-derived growth factor receptor-α on their cell surface are mobilized in response to demyelination [49,[51][52][53]. Recent studies provided the definitive proof that these cells are indeed the main remyelinating cell in the CNS following a demyelinating injury [54,55]. In addition, neural precursor cells (NPCs) of the adult SVZ expressing the embryonic polysialylated form of the neural cell adhesion molecule (PSA-NCAM) react to inflammation and demyelination with proliferation, and migration into the tissue and glial differentiation, generating both astrocytes and remyelinating oligodendrocytes [56][57][58][59].…”

Myelin Regeneration in Multiple Sclerosis: Targeting Endogenous Stem Cells

“…In the adult CNS, these cells are both selfrenewing and multipotent, having been observed to give rise to certain neurons, astrocytes (albeit rarely), and Schwann cells, as well as oligodendrocytes in vivo, and so can reasonably be regarded as a type of adult neural stem cell [22][23][24][25]. The response to demyelination causes OPCs to become activated, a morphological change accompanied by upregulation of genes not normally expressed in the resting state [26][27][28][29].…”