The effects of heavy-ion radiation on translational regulation of circulatory homeostasis in the hypothalamus

We set out to study unexplored biological effects of heavy-ion radiation on brain function. We hypothesized that heavy-ion radiation impairs brain function at the level of protein translation. We tested this hypothesis using our unique mouse line, deficient in the neuronal mRNA-specific binding protein CAGER (CAGER-2-knockout mice). We performed 56Fe-heavy ion irradiation (0.5 Gy and 1.0 Gy) on mouse brains in vivo and analyzed the protein expression in various subregions of the brain, at 3 hrs and at 30 hrs post-irradiation. We have demonstrated that some of key factors in the brain function were down-regulated in CAGER-2-KO mice, but this down-regulation was not observed in wild type mice. Our findings show that neurons indeed respond to heavy-ion radiation at the protein level. The preliminary data point up the significance of the CAGER-KO mice as a mouse model to examine the totally novel aspect of the biological effect of heavy-ion irradiation on the central nervous system. We must analyze the levels of damage to DNA and mRNAs in the same mice models, in order to determine the response of the brain to heavy-ion radiation at the level of mRNA translation in vivo. (author)