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Differential recovery of neural stem cells in the subventricular zone and dentate gyrus after ionizing radiation.

Journal article
Authors Nina Hellström
Thomas Björk-Eriksson
Klas Blomgren
Hans-Georg Kuhn
Published in Stem cells (Dayton, Ohio)
Volume 27
Issue 3
Pages 634-641
ISSN 1549-4918
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Clinical Sciences
Pages 634-641
Language en
Links dx.doi.org/10.1634/stemcells.2008-0...
Keywords neural stem/progenitor cells, neurogenesis, stem cell niche, hippocampus, subventricular zone, ionizing radiation
Subject categories Medical and Health Sciences, Cell and Molecular Biology

Abstract

Radiation therapy is a widely used treatment for malignant CNS tumors. Mature neurons are terminally differentiated, whereas stem and progenitor cells have a prominent proliferative capacity and are therefore highly vulnerable to irradiation. Our aim was to investigate how cranial radiation in young rats would affect stem/progenitor cells in the two niches of adult neurogenesis, the subventricular zone (SVZ) and the dentate gyrus of the hippocampal formation. Nine weeks after irradiation we found that in irradiated animals, hippocampal neurogenesis was reduced to 5% of control levels. Similarly, the number of actively proliferating cells and radial glia-like stem cells (nestin+/GFAP+) in the dentate gyrus, was reduced to 10% and 15% of control levels, respectively. In the irradiated olfactory bulb, neurogenesis was reduced to 40% of control levels and the number of actively proliferating cells in the SVZ was reduced to 53% of control levels. However, the number of nestin+/GFAP+ cells in the SVZ was unchanged compared to controls. To evaluate the immediate response to the radiation injury we quantified the amount of proliferation in the SVZ and dentate gyrus one day after irradiation. We found an equal reduction in proliferating cells both in dentate gyrus and SVZ. In summary, we show an initial response to radiation injury that is similar in both brain stem cell niches. However, the long-term effects on stem cells and neurogenesis in these two areas differ significantly, where the dentate gyrus is severely affected long-term, whereas the SVZ appears to recover with time. ______________________________________________________________________________

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