Activation of the subventricular zone in multiple sclerosis: Evidence for early glial progenitors
Brahim Nait-Oumesmar,Nathalie Picard-Riera,Christophe Kerninon,Laurence Decker,Danielle Seilhean,Günter U. Höglinger,Etienne C. Hirsch,Richard Reynolds,Anne Baron-Van Evercooren +8 more
TL;DR: Data indicate that, as in rodents, activation of gliogenesis in the SVZ occurs in MS and suggest the mobilization of SVZ-derived early glial progenitors to periventricular lesions, where they could give rise to oligodendrocyte precursors.
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Abstract: In multiple sclerosis (MS), oligodendrocyte and myelin destruction lead to demyelination with subsequent axonal loss. Experimental demyelination in rodents has highlighted the activation of the subventricular zone (SVZ) and the involvement of progenitor cells expressing the polysialylated form of neural cell adhesion molecule (PSA-NCAM) in the repair process. In this article, we studied the distribution of early PSA-NCAM+ progenitors in the SVZ and MS lesions in human postmortem brains. Compared with controls, MS SVZ showed a 2- to 3-fold increase in cell density and proliferation, which correlated with enhanced numbers of PSA-NCAM+ and glial fibrillary acidic protein-positive (GFAP+) cells. PSA-NCAM+ progenitors mainly were Sox9+, and a few expressed Sox10 and Olig2, markers of oligodendroglial specification. PSA-NCAM+ progenitors expressing Sox10 and Olig2 also were detected in demyelinated MS lesions. In active and chronic active lesions, the number of PSA-NCAM+ progenitors was 8-fold higher compared with chronic silent lesions, shadow plaques, and normal-appearing white matter. In active and chronic active lesions, PSA-NCAM+ progenitors were more frequent in periventricular lesions (30–50%) than in lesions remote from the ventricular wall. These data indicate that, as in rodents, activation of gliogenesis in the SVZ occurs in MS and suggest the mobilization of SVZ-derived early glial progenitors to periventricular lesions, where they could give rise to oligodendrocyte precursors. These early glial progenitors could be a potential target for therapeutic strategies designed to promote myelin repair in MS.
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Citations
Demyelination and Remyelination in Multiple Sclerosis
Lars Bø,Lars Bø,Margaret M. Esiri,Margaret M. Esiri,Nikos Evangelou,Tanja Kuhlmann +5 more
- 01 Jan 2013
TL;DR: The aim of this review is to give a brief account of the histopathology of demyelination and remyelinated in MS, with an emphasis on some issues of current interest in MS pathology research, including MS lesion staging, pathological heterogeneity, gray matter pathology, and axonal loss.
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ApoTransferrin: dual role on adult subventricular zone-derived neurospheres.
TL;DR: Evidence supports a key role of Tf on the generation of OL from NSC/NPCs and highlights its potential in demyelinating disorder treatment.
Developmental dynamics of neurogenesis and gliogenesis in the postnatal mammalian brain in health and disease: Historical and future perspectives
TL;DR: The mature mammalian brain has long been thought to be a structurally rigid, static organ since the era of Ramón y Cajal in the early 20th century, but evidence accumulated over the past three decades has completely overturned this long‐held view and it is known that new neurons and glia are continuously added to the brain at postnatal stages, even in mature adults of various mammalian species, including humans.
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Signalling pathways that inhibit the capacity of precursor cells for myelin repair.
Jennifer K. Sabo,Holly S. Cate +1 more
TL;DR: Neural precursor cells and oligodendrocyte progenitor cells are reviewed and evidence for the functional role of key signalling pathways in inhibiting regeneration from these precursor cell populations is reviewed.
Demyelination-Induced Inflammation Attracts Newly Born Neurons to the White Matter
Samah Kalakh,Abdeslam Mouihate +1 more
TL;DR: Interestingly, blunting brain inflammation led to reduced neurogenesis around the demyelination area and in the SVZ, suggesting that the white matter inflammation creates a conducive environment for the recruitment of newly born neurons.
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