Generation of reactive astrocytes from NG2 cells is regulated by sonic hedgehog
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27340757
DOI
10.1002/glia.23019
Knihovny.cz E-resources
- Keywords
- NG2 cells, astrocytes, glial scar, ischemia, sonic hedgehog,
- MeSH
- Astrocytes metabolism MeSH
- Cell Differentiation physiology MeSH
- Brain Ischemia pathology MeSH
- Brain cytology MeSH
- Mice MeSH
- Neuroglia metabolism MeSH
- Oligodendroglia metabolism MeSH
- Cell Count MeSH
- Brain Injuries pathology MeSH
- Hedgehog Proteins metabolism MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hedgehog Proteins MeSH
- Shh protein, mouse MeSH Browser
NG2 cells, a fourth glial cell type in the adult mammalian central nervous system, produce oligodendrocytes in the healthy nervous tissue, and display wide differentiation potential under pathological conditions, where they could give rise to reactive astrocytes. The factors that control the differentiation of NG2 cells after focal cerebral ischemia (FCI) are largely unknown. Here, we used transgenic Cspg4-cre/Esr1/ROSA26Sortm14(CAG-tdTomato) mice, in which tamoxifen administration triggers the expression of red fluorescent protein (tomato) specifically in NG2 cells and cells derived therefrom. Differentiation potential (in vitro and in vivo) of tomato-positive NG2 cells from control or postischemic brains was determined using the immunohistochemistry, single cell RT-qPCR and patch-clamp method. The ischemic injury was induced by middle cerebral artery occlusion, a model of FCI. Using genetic fate-mapping method, we identified sonic hedgehog (Shh) as an important factor that influences differentiation of NG2 cells into astrocytes in vitro. We also manipulated Shh signaling in the adult mouse brain after FCI. Shh signaling activation significantly increased the number of astrocytes derived from NG2 cells in the glial scar around the ischemic lesion, while Shh signaling inhibition caused the opposite effect. Since Shh signaling modifications did not change the proliferation rate of NG2 cells, we can conclude that Shh has a direct influence on the differentiation of NG2 cells and therefore, on the formation and composition of a glial scar, which consequently affects the degree of the brain damage. GLIA 2016;64:1518-1531.
References provided by Crossref.org
Out of the core: the impact of focal ischemia in regions beyond the penumbra
Reactive gliosis in traumatic brain injury: a comprehensive review
Transient astrocyte-like NG2 glia subpopulation emerges solely following permanent brain ischemia
On the Common Journey of Neural Cells through Ischemic Brain Injury and Alzheimer's Disease
