CELLULAR AND MOLECULAR MARKERS OF NEUROINFLAMMATION AND STATE OF COGNITIVE FUNCTIONS IN A DELAYED PERIOD AFTER PROLONGED γ-, n-IRRADIATION OF MICE AT LOW DOSES

Abstract

The study aimed to investigate the effect of low-dose rate (2.13 mGy/h) prolonged γ,n-irradiation at 0.05 and 0.5 Gy on brain microglia, expression of pro- and anti-inflammatory cytokine genes, behavior and cognition of C57Bl/6 mice two months and one year after exposure. The decrease in the number of resting microglia and the increase in the proportion of activated microglia in brain cell preparations were observed after γ,n-irradiation at a dose of 0.5 Gy. Immunohistochemical analysis revealed the increased number of microglia cells and unaltered number of astrocytes in the hippocampus after γ,n-irradiation at both doses. Expression of TNFα and IL-1β pro-inflammatory cytokine genes in the hippocampus was increased after irradiation at both doses. Expression of TGFβ and IL-4 anti-inflammatory cytokine genes was decreased two months after irradiation only at a dose of 0.5 Gy, suggesting more intensive neuroinflammation. Analysis performed a year later revealed an age-related decrease in the number of resting microglia and increase in proportion of activated microglia compared to young animals, with more profound changes in male mice. The state of microglia in control and irradiated mice was similar one year after exposure. Neither two months nor one year after irradiation the impairments of motor activity and spatial memory of mice were detected; nevertheless, mice irradiated at a dose of 0.5 Gy demonstrated anxious behavior and decreased spatial learning in Morris water maze one year after exposure. In summary, we showed that γ, n-irradiation at doses of 0.05 and 0.5 Gy induced neuroinflammation two months after exposure. No difference from the control mice was observed one year after irradiation. Disturbances of behavior and spatial memory of irradiated mice were not detected.