Spatial memory and changes in expression of genes of neurotrophic factors in adult rat brain after fractionated whole brain irradiation

Background: Ionizing radiation causes cognitive impairment in adult brain. However, the effects of various irradiation protocols with fractionated fixed total dose on hippocampal function have not yet been studied. Materials and Methods: Fractionated whole brain irradiation with a total dose of 36 Gy was performed according to the following protocols: 2Gy-18 fractions (2Gy*18), 4Gy-9 fraction (4Gy*9) and 6Gy-6 fractions (6Gy*6). Changes in spatial memory were studied in Morris water maze tests at 12th and 17th day after irradiation with a hidden platform and at 38th day after irradiation without a platform. Levels of expression of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) genes were evaluated using qPCR. Results: Expression of genes of neurotrophic factors (BDNF and VEGF) was decreased at 4th and 8th week after irradiation, the decrease depended on fractionation. The Morris water maze test with a hidden platform showed improvement in long-term spatial memory at 12th and 17th day after irradiation. In the Morris water maze test without platform cognitive deficit was detected only in 6Gy*6 group at 4th week after irradiation. Conclusion: Our study shows that different fractionation protocols affect hippocampal functions differently, and that the greatest negative impact has the protocol with the maximum single dose. In addition, decrease in expression of genes of neurotrophic factors might play an important role in cognitive impairment.