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Neurogenesis, exercise, and cognitive late effects of pediatric radiotherapy.

Rodgers SP, Trevino M, Zawaski JA, Gaber MW, Leasure JL - Neural Plast. (2013)

Bottom Line: However, RT damages the brain and disrupts ongoing developmental processes, resulting in debilitating cognitive "late" effects that may take years to fully manifest.These late effects likely derive from a long-term decrement in cell proliferation, combined with a neural environment that is hostile to plasticity, both of which are induced by RT.Potential treatments for cognitive late effects should address both of these conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Houston, Houston, TX 77204, USA.

ABSTRACT
Brain cancer is a common type of childhood malignancy, and radiotherapy (RT) is a mainstay of treatment. RT is effective for tumor eradication, and survival rates are high. However, RT damages the brain and disrupts ongoing developmental processes, resulting in debilitating cognitive "late" effects that may take years to fully manifest. These late effects likely derive from a long-term decrement in cell proliferation, combined with a neural environment that is hostile to plasticity, both of which are induced by RT. Long-term suppression of cell proliferation deprives the brain of the raw materials needed for optimum cognitive performance (such as new neurons in the hippocampus and new glia in frontal cortex), while chronic inflammation and dearth of trophic substances (such as growth hormone) limit neuroplastic potential in existing circuitry. Potential treatments for cognitive late effects should address both of these conditions. Exercise represents one such potential treatment, since it has the capacity to enhance cell proliferation, as well as to promote a neural milieu permissive for plasticity. Here, we review the evidence that cognitive late effects can be traced to RT-induced suppression of cell proliferation and hostile environmental conditions, as well as emerging evidence that exercise may be effective as an independent or adjuvant therapy.

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Effect of a single 4 Gy dose of X-ray radiation on microglia in the developing rat brain 24 hr after exposure. (a, b) A schematic representation of microglia distribution (gray dots) in the cerebral cortex showing that RT-induced loss of microglia is more pronounced in inner layers relative to superficial layers. (c, d) Representative 20x images of Iba1+ staining in the retrosplenial cortex showing that RT not only reduces the number of microglia but also alters their morphology.
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fig6: Effect of a single 4 Gy dose of X-ray radiation on microglia in the developing rat brain 24 hr after exposure. (a, b) A schematic representation of microglia distribution (gray dots) in the cerebral cortex showing that RT-induced loss of microglia is more pronounced in inner layers relative to superficial layers. (c, d) Representative 20x images of Iba1+ staining in the retrosplenial cortex showing that RT not only reduces the number of microglia but also alters their morphology.

Mentions: Recent research has begun to elucidate the important role that microglia have in maintaining the neurogenic niche [106–108]. Unfortunately, radiation severely disrupts microglial distribution, alters their morphology (see Figure 6), and decreases their numbers [109], effects that likely contribute to RT-induced neurogenesis impairment. It has been shown that, after radiation, microglia in the SVZ rebound more quickly than those in the DG. This may explain why neurogenesis recovers better in the SVZ, compared to the dentate [110]. Voluntary exercise has been shown to increase microglia [111], suggesting a further means by which exercise could help to restore a microenvironment conducive to cell proliferation.


Neurogenesis, exercise, and cognitive late effects of pediatric radiotherapy.

Rodgers SP, Trevino M, Zawaski JA, Gaber MW, Leasure JL - Neural Plast. (2013)

Effect of a single 4 Gy dose of X-ray radiation on microglia in the developing rat brain 24 hr after exposure. (a, b) A schematic representation of microglia distribution (gray dots) in the cerebral cortex showing that RT-induced loss of microglia is more pronounced in inner layers relative to superficial layers. (c, d) Representative 20x images of Iba1+ staining in the retrosplenial cortex showing that RT not only reduces the number of microglia but also alters their morphology.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649702&req=5

fig6: Effect of a single 4 Gy dose of X-ray radiation on microglia in the developing rat brain 24 hr after exposure. (a, b) A schematic representation of microglia distribution (gray dots) in the cerebral cortex showing that RT-induced loss of microglia is more pronounced in inner layers relative to superficial layers. (c, d) Representative 20x images of Iba1+ staining in the retrosplenial cortex showing that RT not only reduces the number of microglia but also alters their morphology.
Mentions: Recent research has begun to elucidate the important role that microglia have in maintaining the neurogenic niche [106–108]. Unfortunately, radiation severely disrupts microglial distribution, alters their morphology (see Figure 6), and decreases their numbers [109], effects that likely contribute to RT-induced neurogenesis impairment. It has been shown that, after radiation, microglia in the SVZ rebound more quickly than those in the DG. This may explain why neurogenesis recovers better in the SVZ, compared to the dentate [110]. Voluntary exercise has been shown to increase microglia [111], suggesting a further means by which exercise could help to restore a microenvironment conducive to cell proliferation.

Bottom Line: However, RT damages the brain and disrupts ongoing developmental processes, resulting in debilitating cognitive "late" effects that may take years to fully manifest.These late effects likely derive from a long-term decrement in cell proliferation, combined with a neural environment that is hostile to plasticity, both of which are induced by RT.Potential treatments for cognitive late effects should address both of these conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Houston, Houston, TX 77204, USA.

ABSTRACT
Brain cancer is a common type of childhood malignancy, and radiotherapy (RT) is a mainstay of treatment. RT is effective for tumor eradication, and survival rates are high. However, RT damages the brain and disrupts ongoing developmental processes, resulting in debilitating cognitive "late" effects that may take years to fully manifest. These late effects likely derive from a long-term decrement in cell proliferation, combined with a neural environment that is hostile to plasticity, both of which are induced by RT. Long-term suppression of cell proliferation deprives the brain of the raw materials needed for optimum cognitive performance (such as new neurons in the hippocampus and new glia in frontal cortex), while chronic inflammation and dearth of trophic substances (such as growth hormone) limit neuroplastic potential in existing circuitry. Potential treatments for cognitive late effects should address both of these conditions. Exercise represents one such potential treatment, since it has the capacity to enhance cell proliferation, as well as to promote a neural milieu permissive for plasticity. Here, we review the evidence that cognitive late effects can be traced to RT-induced suppression of cell proliferation and hostile environmental conditions, as well as emerging evidence that exercise may be effective as an independent or adjuvant therapy.

Show MeSH
Related in: MedlinePlus