Effects of p21 on adult hippocampal neuronal development after irradiation

Cell Death Discovery
Yu-Qing Li, Chong Shun Wong

Abstract

Inhibition of hippocampal neurogenesis is implicated in neurocognitive impairment after cranial irradiation. We recently demonstrated that disruption of neuronal development after DNA damage was regulated by p53. The cyclin-dependent kinase inhibitor 1 or p21, a downstream effector p53, mediates cell cycle arrest in response to DNA damage. There is evidence that p21 negatively regulates proliferation of neural progenitors (NPCs). Here we characterized the effects of p21 on disruption of neuronal development in the hippocampal dentate gyrus after irradiation. We irradiated young adult mice wild type (+/+) or knockout (-/-) of the Cdkn1a (p21) gene, and used different bromodeoxyuridine (BrdU) paradigms for cell fate mapping. The acute apoptotic response of NPCs in the subgranular zone of the dentate gyrus was independent of p21 after irradiation. In nonirradiated mice, p21 knockout resulted in an increase in neuroblast proliferation and neurogenesis. At 9 weeks after 5Gy, NPCs in the subgranular zone demonstrated increased p21 expression. Loss of newborn type-1 cells and disruption of hippocampal neurogenesis was evident at 9 weeks after irradiation, and these effects were independent of p21 genotype status. Within the developmen...Continue Reading

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Citations

Jul 15, 2020·International Journal of Molecular Sciences·Maria Victoria Niklison-ChirouGerry Melino
May 10, 2019·Frontiers in Cell and Developmental Biology·Anja Urbach, Otto W Witte
Mar 12, 2021·Journal of Neuropathology and Experimental Neurology·Yu-Qing Li, C Shun Wong

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