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In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation
journal contribution
posted on 2023-06-09, 14:34 authored by Penny Jeggo, Lara BarazzuolThe embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis.
Funding
RISK-IR: Risk, stem cells and tissue kinetics - Ionising radiation (HPA lead); G1009; EUROPEAN UNION; 323267
History
Publication status
- Published
File Version
- Published version
Journal
Journal of Radiation ResearchISSN
0449-3060Publisher
Oxford Univeristy PressExternal DOI
Issue
S1Volume
57Page range
i2-i10Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-08-16First Open Access (FOA) Date
2018-08-16First Compliant Deposit (FCD) Date
2018-08-15Usage metrics
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