INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Le, O; Palacio, L; Bernier, G; Batinic-Haberle, I; Hickson, G; Beauséjour, C

Published Date

  • June 5, 2018

Published In

Volume / Issue

  • 10 / 6

Start / End Page

  • 1721 - 1733

PubMed ID

  • 29706499

Pubmed Central ID

  • PMC5989693

Electronic International Standard Serial Number (EISSN)

  • 2213-6711

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2018.03.025


  • eng

Conference Location

  • United States