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Protecting Brainpower During Radiation

July 8, 2011 | Leigh MacMillan

Cranial irradiation to treat brain cancers often has long-term negative neurocognitive effects, including lowered IQ, learning difficulties and memory loss, especially in the pediatric population.

Fen Xia, M.D., Ph.D., and colleagues have reported that these effects may be due to radiation-induced damage to the hippocampus, the brain region responsible for learning and memory. They previously demonstrated that inhibition of the protein GSK3β (glycogen synthase kinase 3β) reduces radiation-induced hippocampal neuron cell death and protects neurocognitive function in mice treated with cranial irradiation.

The team has now discovered that inhibition of GSK3β – with specific inhibitors or using genetic manipulations – accelerates the repair of radiation-induced DNA damage (double strand breaks) in normal hippocampal neurons, but not in malignant glioma cells. The findings, reported in the May issue of Neuro-Oncology, link GSK3β to DNA repair pathways and suggest novel targets for the development of neuroprotective drugs to use during whole brain irradiation. In particular, the research suggests that GSK3β inhibitors may have neuroprotective effects.