Journal
BIOLOGY OPEN
Volume 4, Issue 8, Pages 980-992Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.012773
Keywords
Adult neural stem cells; Subventricular zone; Oligodendrocyte precursors; Myelin regeneration
Categories
Funding
- CNRS, Aix Marseille University
- French National Research Agency [ANR-11-BSV4-012-01]
- French competitiveness cluster EuroBioMed
- Agence Nationale de la Recherche [ANR-10-INSB-04-01]
Ask authors/readers for more resources
Myelin regeneration can occur in the brain following demyelination. Parenchymal oligodendrocyte progenitors (pOPC) are known to play a crucial role in this process. Neural stem cells (NSC) residing in the ventricular-subventricular zone (V-SVZ) also have the ability to generate oligodendrocytes but their contribution to endogenous myelin repair was so far considered to be negligible. Here, we addressed the relative contribution of pOPC and V-SVZ-derived neural progenitors (SVZdNP) to remyelination in cuprizone mouse models of acute or chronic corpus callosum (CC) demyelination. Using genetic tracing, we uncover an unexpected massive and precocious recruitment of SVZdNP in the anterior CC after acute demyelination. These cells very quickly adopt an oligodendrocytic fate and robustly generate myelinating cells as efficiently as pOPC do. In more posterior areas of the CC, SVZdNP recruitment is less important whereas pOPC contribute more, underlining a regionalization in the mobilization of these two cell populations. Strikingly, in a chronic model when demyelination insult is sustained in time, SVZdNP minimally contribute to myelin repair, a failure associated with a depletion of NSC and a drastic drop of progenitor cell proliferation in V-SVZ. In this context, pOPC remain reactive, and become the main contributors to myelin regeneration. Altogether our results highlight a region and context-dependent contribution of SVZdNP to myelin repair that can equal pOPC. They also raise the question of a possible exhaustion of V-SVZ proliferation potential in chronic pathologies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available