Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 38, Pages 14632-14637Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0711128105
Keywords
exercise; juvenile; open field; radiotherapy; stem cell
Categories
Funding
- Swedish Research Council
- Swedish Childhood Cancer Foundation
- King Gustav V Jubilee Clinic Research Foundation
- Frimurare Barnhus Foundation, Swedish
- Wilhelm and Martina Lundgren Foundation
- Edit Jacobssons Fund
- Soderberg Foundation, Adlerbertska Forskningsstiftelsen
- MS-forenings Forsknings-och Byg-gnadsfonder, Stiflesen Goljesminne
- Swedish Brain Foundation
- Goteborg Medical Society
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Cranial radiation therapy is commonly used in the treatment of childhood cancers. it is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.
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