title: Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus.
abstract: Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada. yqli@sri.utoronto.ca.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada. zoey.cheng@mail.utoronto.ca.|Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada. zoey.cheng@mail.utoronto.ca.
authors.forename: Zoey
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada. shun.wong@sunnybrook.ca.|Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada. shun.wong@sunnybrook.ca.|Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, ON M4N 3M5, Canada. shun.wong@sunnybrook.ca.
authors.forename: Shun
authors.initials: S
authors.lastname: Wong
mesh_terms: D000818:Animals; D017209:Apoptosis; D064032:Calbindin 2 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D055495:Neurogenesis; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D064032:Calbindin 2; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016159:Tumor Suppressor Protein p53
keywords: apoptosis; dentate gyrus; irradiation; neural progenitors; neural stem cells; p53