Ricerc@Sapienza

Exposure of the developing or adult brain to ionizing radiation (IR) can cause cognitive impairment and/
or brain cancer, by targeting neural stem/progenitor cells (NSPCs). IR effects on NSPCs include transient
cell cycle arrest, permanent cell cycle exit/differentiation, or cell death, depending on the experimental
conditions. In vivo studies suggest that brain age influences NSPC response to IR, but whether this is
due to intrinsic NSPC changes or to niche environment modifications remains unclear. Here, we describe
the dose-dependent, time-dependent effects of X-ray IR in NSPC cultures derived from the mouse
foetal cerebral cortex. We show that, although cortical NSPCs are resistant to low/moderate IR doses,
high level IR exposure causes cell death, accumulation of DNA double-strand breaks, activation of p53-
related molecular pathways and cell cycle alterations. Irradiated NSPC cultures transiently upregulate
differentiation markers, but recover control levels of proliferation, viability and gene expression in the
second week post-irradiation. These results are consistent with previously described in vivo effects of IR
in the developing mouse cortex, and distinct from those observed in adult NSPC niches or in vitro adult
NSPC cultures, suggesting that intrinsic differences in NSPCs of different origins might determine, at
least in part, their response to IR.