Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain

Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14632-7. doi: 10.1073/pnas.0711128105. Epub 2008 Sep 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / radiation effects
  • Cell Proliferation / radiation effects
  • Cranial Irradiation*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology
  • Gene Expression Regulation
  • Hippocampus / cytology*
  • Hippocampus / radiation effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / genetics
  • Neurons / cytology*
  • Neurons / metabolism
  • Neurons / radiation effects*
  • Neuropeptides / genetics
  • Running / physiology*
  • Stem Cells / cytology

Substances

  • Microtubule-Associated Proteins
  • Neuropeptides
  • doublecortin protein