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

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.exercise ͉ juvenile ͉ open field ͉ radiotherapy ͉ stem cell

Irradiation to the Young Mouse Brain Caused Long-Term, Progressive Depletion of Neurogenesis but did not Disrupt the Neurovascular Niche

“…We also confirmed and extended previous studies reporting that irradiation reduces the pool of neural progenitor cells and leads to a persistently decreased level of neurogenesis. 16,23,25,27,28 In addition, we verify both the natural decline in hippocampal neurogenesis with age, 29 as well as clearly demonstrate the detrimental effect of irradiation on immature neurons, such that neurogenesis deteriorated more decreased at 7 weeks (P63), and 98% decreased at 1 year after irradiation). Representative pictures depicting the DCX staining 7 weeks after irradiation in control (B) and irradiated (C) animals.…”

Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells

“…While some data exist showing that such impairments can be ameliorated in part by voluntary running (26), this report shows that hESC transplantation can be effectively used to reduce a serious complication of cranial irradiation. The mechanism of this cell-mediated effect is not yet clear, and whether it depends on cell replacement per se, as opposed to trophic support provided by the transplanted cells, remains to be determined.…”

Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training

“…34 Animal models show that exercise increases gliogenesis, angiogenesis, and neurogenesis in neural precursor niches as well as the production of neurotrophic molecules involved in the protection and promotion of cell survival, neurite outgrowth, and synaptic plasticity. By harnessing these endogenous processes, exercise promotes brain recovery in rodent models of hypoxia, 35 radiation, 36 and traumatic brain injury. 37 Consistent with this, we found that increased fitness levels were significantly and marginally related to decreased RT and increased hippocampal volume, respectively.…”