Early and long-term effects of low- and high-LET radiation on rat behavior and monoamine metabolism in different brain regions

Space radiation is one of the factors representing a significant health risk to the astronauts during deep-space missions. A most harmful component of space radiation beyond the Earth's magnetosphere is the galactic cosmic rays which are composed of high-energy protons, α particles, and high charge and energy (HZE) nuclei. Recent studies performed at particle accelerators have revealed a significant impact of HZE nuclei on the central nervous system and, in particular, on the cognitive functions. However the exact molecular mechanisms behind the observed impairments remain mostly unclear. This research is focused on study of early and long-term effects of low- and high-linear-energy-transfer (LET) radiation on the rat behavior and monoamine metabolism in the brain regions involved in behavior and motor control and form emotional and motivational states. Different groups of rats were whole-body exposed to 500 MeV/u (12) C particles (LET 10.6 keV/µm) available at the Nuclotron accelerator of the Joint Institute for Nuclear Research (Dubna, Russia) and to gamma rays at the equivalent dose of 1 Gy. An additional group of animals was sham-irradiated and considered as a control. The isolated brain regions have included the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum where we determined the concentrations of noradrenalin, dopamine and its metabolites 3,4-doxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine and serotonin and its metabolite 5-hydroxyindoleacetic acid. The following effects were observed in the different periods after irradiation. 1 day after exposure to (12) C particles strong changes in the concentration of monoamines and their metabolites were observed in three structures, namely, the prefrontal cortex, nucleus accumbens, and hippocampus. However, significant changes were found in the prefrontal cortex and weaker changes were seen in the nucleus accumbens, whereas changes were insignificant in the hippocampus. The experiments revealed the high sensitivity and reactivity of the prefrontal cortex, which we relate to the key role of this structure in essential processes of behavior. 30 days after irradiation with (12) C particles and gamma rays behavioral reactions of rats were evaluated by the open field test. The measurements have revealed differences between the effects observed after irradiation with HZE nuclei and gamma-rays at the same dose. The effect of accelerated carbon ions consisted in increasing motion activity measured as the number of sector border crossings and inhibiting exploratory activity of the animals estimated by burrowing, while gamma-irradiation had a significant impact only on the latter index. The rats' total activity increased by 18% after irradiation with (12) C ions, but exposure to gamma rays caused no significant differences from the control values. However the changes in total activity index after sparsely and densely ionizing radiations were also significant. In parallel to the analysis of monoamine metabolism, exploratory behavior, and general activity, some other immunohematological criteria were estimated on the 30th day after exposure to (12) C particles and gamma rays. The significant differences between the HZE-, gamma-irradiated, and control groups were found in the bone marrow cellularity. The changes in spleen mass were significant only between control and each of irradiated group whereas effects of (12) C and gamma rays were near the same. The similar difference was observed for the number of leucocytes in peripheral blood.