Inhibition of hippocampal neurogenesis is implicated in neurocognitive dysfunction after cranial irradiation for brain tumors. How irradiation results in impaired neuronal development remains poorly understood. The Trp53 (p53) gene is known to regulate cellular DNA damage response after irradiation. Whether it has a role in disruption of late neuronal development remains unknown. Here we characterized the effects of p53 on neuronal development in adult mouse hippocampus after irradiation. Different bromodeoxyuridine incorporation paradigms and a transplantation study were used for cell fate mapping. Compared with wild-type mice, we observed profound inhibition of hippocampal neurogenesis after irradiation in mice deficient in p53 despite the absence of acute apoptosis of neuroblasts. The putative neural stem cells were apoptosis resistant after irradiation regardless of p53 genotype. Cell fate mapping using different bromodeoxyuridine incorporation paradigms revealed enhanced activation of neural stem cells and their consequential exhaustion in the absence of p53 after irradiation. Both p53-knockout and wild-type mice demonstrated similar extent of microglial activation in the hippocampus after irradiation. Impairment of neuronal differentiation of neural progenitors transplanted in irradiated hippocampus was not altered by p53 genotype of the recipient mice. We conclude that by inhibiting neural progenitor activation, p53 serves to mitigate disruption of neuronal development after irradiation independent of apoptosis and perturbation of the neural stem cell niche. These findings suggest for the first time that p53 may have a key role in late effects in brain after irradiation.

ABSTRACT. Moso bamboo is a large woody bamboo with the highest ecological, economic, and cultural value among all bamboos in Asia. However, environmental stress influences its growth and development and limits its geographic distribution. Therefore, improving its resistance to environmental stress is extremely important. Dehydration responsive element binding (DREB) transcription factors perform an important role in the regulation of stress-related genes, enhancing the resistance of plants to abiotic stress. In the current study, two novel DREB genes, PeDREB2A and PeDREB1A (Gene ID No. PH01000046G1730 and PH01000668G0350), were isolated from moso bamboo and the sequences were identified and characterized (coding sequence lengths were 795 and 825 bp, respectively). The PeDREB2A and PeDREB1A proteins were estimated to have typical AP2/ERF domains, molecular weights of 28.96 and 28.84 kDa, and isoelectric points of 9.47 and 5.34, respectively.