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Int. J. Mol. Sci. 2016, 17(6), 970; doi:10.3390/ijms17060970

Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

1
,
1,2
and
1,2,3,*
1
Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
2
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
3
Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, ON M4N 3M5, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Received: 13 May 2016 / Revised: 1 June 2016 / Accepted: 13 June 2016 / Published: 20 June 2016
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
View Full-Text   |   Download PDF [5241 KB, uploaded 20 June 2016]   |  

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. View Full-Text
Keywords: neural progenitors; neural stem cells; apoptosis; irradiation; dentate gyrus; p53 neural progenitors; neural stem cells; apoptosis; irradiation; dentate gyrus; p53
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Li, Y.-Q.; Cheng, Z.; Wong, S. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus. Int. J. Mol. Sci. 2016, 17, 970.

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