Combined Ionizing Radiation Exposure by Gamma Rays and Carbon-12 Nuclei Increases Neurotrophic Factor Content and Prevents Age-Associated Decreases in the Volume of the Sensorimotor Cortex in Rats.

In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.14 Gy carbon-12 nuclei) on the locomotor and exploratory activity of rats, and assessed the sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week and 7 months post-irradiation. The sensorimotor cortex tissues were processed to determine whether the behavioral and morphologic effects were associated with changes in neurotrophin content. The irradiated rats were characterized by increased locomotor and exploratory activity, as well as novelty-seeking behavior, at 3 days post-irradiation. At the same time, only unirradiated rats experienced a significant decrease in the sensorimotor cortex volume at 7 months. While there were no significant differences at 1 week, at 7 months, the irradiated rats were characterized by higher neurotrophin-3 and neurotrophin-4 content in the sensorimotor cortex. Thus, IR prevents the age-associated decrease in the sensorimotor cortex volume, which is associated with neurotrophic and neurogenic changes. Meanwhile, IR-induced increases in locomotor activity may be the cause of the observed changes.

Dynamics of Dopamine and Other Monoamines Content in Rat Brain after Single Low-Dose Carbon Nuclei Irradiation.

Space radiation, presented primarily by high-charge and -energy particles (HZEs), has a substantial impact on the central nervous system (CNS) of astronauts. This impact, surprisingly, has not only negative but also positive effects on CNS functions. Despite the fact that the mechanisms of this effect have not yet been elucidated, several studies indicate a key role for monoaminergic networks underlying these effects. Here, we investigated the effects of acute irradiation with 450 MeV/n carbon (12C) nuclei at a dose of 0.14 Gy on Wistar rats; a state of anxiety was accessed using a light-dark box, spatial memory in a Morris water maze, and the dynamics of monoamine metabolism in several brain morphological structures using HPLC. No behavioral changes were observed. Irradiation led to the immediate suppression of dopamine turnover in the prefrontal cortex, hypothalamus, and striatum, while a decrease in the level of norepinephrine was detected in the amygdala. However, these effects were transient. The deferred effect of dopamine turnover increase was found in the hippocampus. These data underscore the ability of even low-dose 12C irradiation to affect monoaminergic networks. However, this impact is transient and is not accompanied by behavioral alterations.

Neurokinin-1 Receptor Antagonist Reverses Functional CNS Alteration Caused by Combined γ-rays and Carbon Nuclei Irradiation.

BACKGROUND: Ionizing Radiation (IR) is one of the major limiting factors for human deep-space missions. Preventing IR-induced cognitive alterations in astronauts is a critical success factor. It has been shown that cognitive alterations in rodents can be inferred by alterations of a psycho- emotional balance, primarily an anxiogenic effect of IR. In our recent work, we hypothesized that the neurokinin-1 (NK1) receptor might be instrumental for such alterations. OBJECTIVE: The NK1 receptor antagonist rolapitant and the classic anxiolytic diazepam (as a comparison drug) were selected to test this hypothesis on Wistar rats. METHODS: Pharmacological substances were administered through intragastric probes. We used a battery of tests for a comprehensive ethological analysis. High-performance liquid chromatography was applied to quantify monoamines content. An analysis of mRNA expression was performed by real-time PCR. Protein content was studied by the Western blotting technique. RESULTS: Our salient finding includes no substantial changes in anxiety, locomotor activity and cognitive abilities of treated rats under irradiation. No differences were found in the content of monoamines. We discovered a synchronous effect on mRNA expression and protein content of 5- HT2a and 5-HT4 receptors in the prefrontal cortex, as well as decreased content of serotonin transporter and increased content of tryptophan hydroxylase in the hypothalamus of irradiated rats. Rolapitant affected the protein amount of a number of serotonin receptors in the amygdala of irradiated rats. CONCLUSION: Rolapitant may be the first atypical radioprotector, providing symptomatic treatment of CNS functional disorders in astronauts caused by IR.

DNA damage in blood leukocytes from mice irradiated with accelerated carbon ions with an energy of 450 MeV/nucleon.

PURPOSE: The objective of the study was to estimate the DNA damage in blood leukocytes at long terms after irradiation of mice with carbon ions (450 MeV/nucleon) both before and in the Bragg peak. MATERIALS AND METHODS: White outbred SHK male mice were exposed to whole-body irradiation with carbon ions at doses of 0.1-2 Gy in the spread-out Bragg peak and at a dose of 6 Gy before and in the Bragg peak. At different times after irradiation (1-75 days), whole blood was collected from the tail of each mouse and analyzed by the comet assay. Mice X-irradiated in the same dose range served as a positive control. The level of the expression of mRNA of CDKN1A, APEX1, BBC3, TXN2, and ß-ACT genes in bone marrow cells was determined in animals irradiated with carbon ions at doses of 0.1-2 Gy using the real-time PCR. RESULTS: It was found that, 24 h after 12C-irradiation, a dose-dependent (0.1-2 Gy) increase in the DNA damage of leukocytes occurred, which was accompanied by a decrease in their concentration and an increase in the expression of the CDKN1A and BBC3 genes in bone marrow cells. The expression of the APEX1 and TXN2 genes did not change. In mice 12C-irradiated at a dose of 6 Gy before and in the Bragg peak, the level of DNA damage changed as follows: by day 3, it increased; by day 23 it returned to the control level; by day 30, it increased again; and by day 75, it fell to the control level on irradiation before the Bragg peak and was significantly higher (p < .05) than in the control after irradiation in the Bragg peak. CONCLUSIONS: The dynamics of changes in the level of DNA damage in leucocytes of 12C-irradiated mice within 30 days is similar to that in mice exposed to sublethal doses of X-radiation. The retention of the high level of DNA damage by day 75 after 12C-irradiation in the Bragg peak indicates a significant injury of cells from different cell pools of the blood system. The high level of DNA damage may be related not only to complex DNA injuries but also to chronic oxidative stress.