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INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice
Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989693/ https://www.ncbi.nlm.nih.gov/pubmed/29706499 http://dx.doi.org/10.1016/j.stemcr.2018.03.025 |
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author | Le, Oanh Palacio, Lina Bernier, Gilbert Batinic-Haberle, Ines Hickson, Gilles Beauséjour, Christian |
author_facet | Le, Oanh Palacio, Lina Bernier, Gilbert Batinic-Haberle, Ines Hickson, Gilles Beauséjour, Christian |
author_sort | Le, Oanh |
collection | PubMed |
description | Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain. Here, we found that exposure to IR leads to persistent DNA damage and the expression of p16INK4a in the hippocampus and subventricular zone regions. This was accompanied by a decline in neurogenesis, as determined by doublecortin expression and bromodeoxyuridine incorporation, an effect partially restored in Ink4a/arf-null mice. Increased neurogenesis in the absence of INK4a/ARF expression was independent of apoptosis and activation of the microglia. Moreover, treatment of irradiated mice with a superoxide dismutase mimetic or clearance of p16INK4a-expressing cells using mouse genetics failed to increase neurogenesis. In conclusion, our results suggest that IR-induced p16INK4a expression is a mechanism that limits neurogenesis. |
format | Online Article Text |
id | pubmed-5989693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-59896932018-06-07 INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice Le, Oanh Palacio, Lina Bernier, Gilbert Batinic-Haberle, Ines Hickson, Gilles Beauséjour, Christian Stem Cell Reports Article Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain. Here, we found that exposure to IR leads to persistent DNA damage and the expression of p16INK4a in the hippocampus and subventricular zone regions. This was accompanied by a decline in neurogenesis, as determined by doublecortin expression and bromodeoxyuridine incorporation, an effect partially restored in Ink4a/arf-null mice. Increased neurogenesis in the absence of INK4a/ARF expression was independent of apoptosis and activation of the microglia. Moreover, treatment of irradiated mice with a superoxide dismutase mimetic or clearance of p16INK4a-expressing cells using mouse genetics failed to increase neurogenesis. In conclusion, our results suggest that IR-induced p16INK4a expression is a mechanism that limits neurogenesis. Elsevier 2018-04-26 /pmc/articles/PMC5989693/ /pubmed/29706499 http://dx.doi.org/10.1016/j.stemcr.2018.03.025 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Le, Oanh Palacio, Lina Bernier, Gilbert Batinic-Haberle, Ines Hickson, Gilles Beauséjour, Christian INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice |
title | INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice |
title_full | INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice |
title_fullStr | INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice |
title_full_unstemmed | INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice |
title_short | INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice |
title_sort | ink4a/arf expression impairs neurogenesis in the brain of irradiated mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989693/ https://www.ncbi.nlm.nih.gov/pubmed/29706499 http://dx.doi.org/10.1016/j.stemcr.2018.03.025 |
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