Journal
EXPERIMENTAL NEUROLOGY
Volume 247, Issue -, Pages 402-409Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2013.01.006
Keywords
IntelliCage; Irradiation; Neurogenesis; Gliosis; Learning; Memory
Categories
Funding
- Swedish Research Council
- Swedish Childhood Cancer Foundation
- King Gustav V Jubilee Clinic Cancer Research Foundation
- Swedish governmental grants
- Frimurare Barnhus Foundation
- Wilhelm and Martina Lundgren Foundation
- Gothenburg Medical Society
- Edit Jacobson's Foundation
- Sahlgrenska Foundations
- Aina Wallstrom's and Mary-Ann Sjoblom's Foundation
- Ulla and Rune Amlov Foundation
- AFA Insurance
- Swedish Society of Medicine
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Radiotherapy is a major cause of long-term complications in survivors of pediatric brain tumors. These complications include intellectual and memory impairments as well as perturbed growth and puberty. We investigated the long-term effects of a single 8 Gy irradiation dose to the brains of 14-day-old mice. Behavior was assessed one year after irradiation using IntelliCage and open field, followed by immunohistochemical investigation of proliferation and neurogenesis in the dentate gyrus of the hippocampus. We found a 61% reduction in proliferation and survival (BrdU incorporation 4 weeks prior to sacrifice), 99% decrease in neurogenesis (number of doublecortin-positive cells) and gliosis (12% higher astrocyte density) one year following irradiation. Irradiated animals displayed increased activity in a novel environment but decreased activity in their home cage. Place learning in the IntelliCage was unaffected by irradiation but reversal learning was impaired. Irradiated animals persevered in visiting previously correct corners to a higher extent compared to control animals. Hence, despite the virtual absence of neurogenesis in these old mice, spatial learning could take place. Reversal learning however, where a previous memory was replaced with a new one, was partly impaired. This model is useful to study the so called late effects of radiotherapy to the young brain and to evaluate possible interventions. (C) 2013 Elsevier Inc. All rights reserved.
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