INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice.
Stem Cell Reports
; 10(6): 1721-1733, 2018 06 05.
Article
in En
| MEDLINE
| ID: mdl-29706499
Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain. Here, we found that exposure to IR leads to persistent DNA damage and the expression of p16INK4a in the hippocampus and subventricular zone regions. This was accompanied by a decline in neurogenesis, as determined by doublecortin expression and bromodeoxyuridine incorporation, an effect partially restored in Ink4a/arf-null mice. Increased neurogenesis in the absence of INK4a/ARF expression was independent of apoptosis and activation of the microglia. Moreover, treatment of irradiated mice with a superoxide dismutase mimetic or clearance of p16INK4a-expressing cells using mouse genetics failed to increase neurogenesis. In conclusion, our results suggest that IR-induced p16INK4a expression is a mechanism that limits neurogenesis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Radiation, Ionizing
/
Brain
/
Gene Expression Regulation
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Cyclin-Dependent Kinase Inhibitor p16
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Neurogenesis
Limits:
Animals
Language:
En
Journal:
Stem Cell Reports
Year:
2018
Document type:
Article
Affiliation country:
Canada
Country of publication:
United States