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Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer.

Journal article
Authors Yoshiaki Sato
Noriko Shinjyo
Machiko Sato
Kazuhiro Osato
Changlian Zhu
Marcela Pekna
Hans-Georg Kuhn
Klas Blomgren
Published in Cell Death & Disease
Volume 4
Pages e591
ISSN 2041-4889
Publication year 2013
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Clinical Sciences, Department of Pediatrics
Pages e591
Language en
Keywords Astrogliosis, Differentiation, Grafting, Neurogenesis, Radiotherapy, Transplantation
Subject categories Pediatrics


Ionizing radiation persistently reduces the pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus (DG) of the hippocampus, which may explain some of the learning deficits observed in patients treated with radiotherapy, particularly pediatric patients. A single dose of 8 Gy irradiation (IR) was administered to the brains of postnatal day 14 (P14) C57BL/6 mice and 1.0 × 10(5) bromodeoxyuridine-labeled, syngeneic NSPCs were injected into the hippocampus 1 day, 1 week or 6 weeks after IR. Cell survival and phenotype were evaluated 5 weeks after grafting. When grafted 1 day post-IR, survival and neuronal differentiation of the transplanted NSPCs were lower in irradiated brains, whereas the survival and cell fate of grafted cells were not significantly different between irradiated and control brains when transplantation was performed 1 or 6 weeks after IR. A young recipient brain favored neuronal development of grafted cells, whereas the older recipient brains displayed an increasing number of cells developing into astrocytes or unidentified cells. Injection of NSPCs, but not vehicle, induced astrogliosis and reduced thickness of the dorsal blade of the GCL after 5 months. In summary, we demonstrate that age and interval between IR and grafting can affect survival and differentiation of grafted NSPCs. The observed long-term gliosis and degeneration warrant caution in the context of NSPC grafting for therapeutical purposes.

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