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ABSTRACT
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 a1er irradiation with a hidden pla2orm and at 38th day a1er irradiation without a pla2orm. 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 a1er irradiation, the decrease depended on fractionation. The Morris water maze test with a hidden pla2orm showed improvement in long-term spatial memory at 12th and 17th day a1er irradiation. In the Morris water maze test without pla2orm cognitive deficit was detected only in 6Gy*6 group at 4th week a1er 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.
Keywords: Fract ionated radiat ion, cognit ive dysfunct ion, spat ial memory, VEGF, BDNF.
INTRODUCTION
Ionizing radiation can significantly affect integrative function of central nervous system in adults (1), and of course, on hippocampus-dependent learning and memory (2). It relates to radiation-induced apoptosis of neural immature progenitor cells in the subventricular zone of the lateral ventricles and in the subgranular zone of the hippocampal dentate gyrus (3) and associated with inhibition of hippocampal neurogenesis (2).
Experiments indicate that even relatively small radiation doses are associated with complex changes in gene expression profile (4). Multiple effects of ionizing radiation on the central nervous system, cognition and behavior depend on the resulting total brain radiation dose and the mode of exposure (5). It was identified that cognitive functions changes strongly depend on the time elapsed after irradiation (6).
The link between cognitive impairment and changes in gene expression profile may be mediated...