Archives2021V. 61. №1.pp. 32–43

Article

Cognitive Impairment and Induction of Neuroinflammation in the Late Period after Single Whole Brain γ-Irradiation of Mice

A. S. Zhirnik, O. D. Smirnova, Ju. P. Semochkina, K. D. Shibaeva, A. V. Rodina, M. G. Ratushnjak, and E. Ju. Moskaleva

National Research Center “Kurchatov Institute”, Moscow, Russia

Abstract

Late effects of single head-only γ-irradiation (2 and 8 Gy) on cognitive function and brain microglia in С57ВL/6 mice were studied. Two months, but not one month, after irradiation at doses of 2 and 8 Gy mice demonstrated increased motor activity (distance traveled and velocity) in the open field test, while there were no changes in exploratory behavior (number of rearings and latency for first rearing) compared to controls at these time points. Contextual fear conditioning data suggested unimpaired associative learning and memory in mice 1 and 2 months after exposure to radiation, as judged by the similar duration of freezing among groups on the training day and 24 hours later (on the testing day). Using the Morris water maze, we revealed the spatial memory deficit in mice irradiated at a dose of 8 Gy at 1 and 2 months post irradiation. Nevertheless, no differences in spatial parameters analyzed for control and irradiated mice were detected 6 months post irradiation. It is important to note that head-only irradiation at a lower dose – 2 Gy – did not result in spatial memory deterioration at all time points studied. We observed the sustained decrease in the number of resting and activated microglia in irradiated mouse brain, and the proportion of activated microglia increased after 8 Gy head irradiation, corresponding to the results from cognitive testing. Data obtained in this study suggest that radiation-induced cognitive impairment may be due to neuroinflammation, in which activation of microglia and increase in the proportion of these cells play a key role.

Keywords

γ-radiation, cognitive functions, spatial memory, microglia, activated microglia, neuroinflammation, whole brain irradiation, brain, mice

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