Radiation therapy is a common treatment for adults and children who present with tumours in or close to the brain. In the last 20 years, advances in radiotherapy have significantly improved the prognosis for brain cancer patients. However, the resulting longer survival rates reveal that the therapy has deleterious effects on brain health – even at low doses, radiation leads to cognitive impairments in later life.
These impairments, which include attention deficits and learning disabilities, occur as a result of the effects of radiation on the hippocampus. This structure is known to be crucial for learning and memory, and is one of a few areas of the brain which contains a population of stem cells which continue to generate new neurons throughout life (by a process called neurogenesis). These newborn cells are necessary for memory function, and radiation causes impairments because it reduces their rate of production.
We now know that physical exercise promotes neurogenesis in the hippocampus and that this has beneficial effects, including improvements in cognitive function and slowing of the onset of dementia. And a new study published in the Proceedings of the National Academy of Sciences shows that neurogenesis induced by exercise can also reverse the damage caused by radiation. The findings therefore have important implications for the rehabilitation of children who undergo radiotherapy for brain tumours.
The discovery that the adult human brain retains the ability to generate new cells is one of the biggest breakthroughs of modern neuroscience, and the knowledge that the hippocampus is one of the brain areas in which neurogenesis occurs is of major significance to the treatment of Alzheimer’s Disease and depression. Shrinkage of the hippocampus is observed in both conditions, and so anything that promotes neurogenesis there – such as physical exercise – is likely to ameliorate the symptoms of patients suffering from them.
With this in mind, Andrew Naylor and his colleagues hypothesized that exercise would reduce the effects of radiation on hippocampal neurogenesis and the cognitive impairments associated with it. They first subjected one group of 9-day-old mice to clinically-relevant doses of X-ray irradiation, and another to a sham irradiation prcedure. 3 days later, the animals’ brains were dissected and the slices were injected with a chemical called bromodeoxyuridine (BrdU), which is incorporated into newly-synthesized DNA and can therefore be used to determine the numbers of dividing cells.
As expected, there was a severe reduction (85%) in the number of dividing cells in the hippocampi of those mice exposed to the X-rays, but not the animals exposed to sham irradation. In another set of experiments, the animals were kept in their cages following irradiation and half of them were given a running wheel. 8 weeks later, BrdU and antibody stainingg were used to examine hippocampal neurogenesis and the hippocampal stem cell population, respectively.
These analyses showed that irradiated running mice had a significantly increased number of newborn neurons in comparison to irradiated mice that were not given a running wheel (see above figure). In the latter group of animals, a reduction in the volume of the granule cell layer (GCL) of the hippocampus was also observed, in comparison to the sham-irradiated non-running mice. There was, however, no significant difference in the GCL volume of irradiated running mice compared to the control groups. These findings were reflected in the animals’ behaviour. Various tests showed that irradiated running mice behaved more like sham-irradiated mice than did the non-running irradiated animals.
This study therefore provides strong evidence that voluntary running reverses the deleterious effects of radiation on the brain. In irradiated mice, running increased the number of newly-generated hippocampal cells, apparently by promoting the expansion of the stem cell pool in that part of the brain. The findings indicate that the damage caused by radiotherapy can be compensated for to some extent by exercise. They also suggest that incorporating exercise into a post-radiotherapy rehabilitation regime could significantly improve the long-term diagnosis of paediatric brain cancer patients.
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Naylor, A.S. et al (2008). Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc. Natl. Acad. Sci. 105: 14632-14637. DOI: 10.1073/pnas.0711128105