Medical Radiology and Radiation Safety. 2022. Vol. 67. № 5

DOI: 10.33266/1024-6177-2022-67-5-10-17

A.S. Zhirnik, A.V. Rodina, Yu.P. Semochkina,
O.V. Vysotskaya, O.D. Smirnova, M.G. Ratushnyak,
E.Yu. Moskaleva

COGNITIVE DISTURBANCES AND THE STATE OF BRAIN GLIAL CELLS IN MICE EXPOSED TO FRACTIONATED WHOLE-BRAIN IRRADIATION

National Research Center Kurchatov Institute, Moscow, Russia

Contact person: A.S. Zhirnik, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

Purpose: To investigate the effect of fractionated whole-brain γ-irradiation at a cumulative dose of 20 Gy on cognitive functions, the state of brain glial cells and expression of multiple cytokines in mice 2 months after exposure.

Material and methods: Male C57Bl/6 mice were exposed to fractionated head γ-irradiation with 5 doses of 4 Gy. Two months after irradiation the behavior and cognitive functions of animals were assessed. After isolation of cells from mice brains the content of resting and activated microglia, microglial cells with M1- and M2-phenotype, astrocytes, proliferating cells were evaluated, and the hippocampal mRNA levels of pro- and anti-inflammatory cytokines (TNFα, IL-1β, IL-6, IL-4, TGFβ) were determined.

Results: It was shown that fractionated head γ-irradiation didn’t alter the locomotor activity and associative (context fear) memory, but reduced the episodic memory in novel object recognition test (discrimination index was 0.44 ± 0.08 и 0.02 ± 0.09 in control and irradiated groups, respectively) and spatial memory in Morris water maze (time in target quadrant was 46,8 ± 2,4 % and 37,4 ± 2,8 % in control and irradiated groups, respectively). Exposure of γ-radiation significantly reduced the brain contents of microglial cells (Iba1⁺) and astrocytes (GFAP⁺) with concurrent 2.5 times increase in proportion of activated microglia (from 2.0 ± 0.2 % in control to 4.9 ± 0.5 % in irradiated mice), changed the M1- / M2-microglia ratio and significantly decreased the number of proliferating cells (BrdU⁺) and proliferating microglial cells (BrdU⁺/Iba1⁺). An increase in mRNA level of pro-inflammatory cytokine TNFα, a decrease in mRNA level of anti-inflammatory cytokine TGFβ and concurrent increase in mRNA level of IL-4 were detected in hippocampus 2 months after irradiation.

Conclusion: We show that fractionated head γ-irradiation at a cumulative dose of 20 Gy reduces the episodic and spatial memory in mice 2 months after exposure. Cognitive dysfunctions detected are associated with neuroinflammation characterized by increasing proportion of activated brain microglia and altered hippocampal pro- and anti-inflammatory cytokine profile.

Keywords: brain, hippocampus, microglia, activated microglia, astrocytes, neuroinflammation, cytokines, gene expression, fractionated irradiation, cognitive function, mice

For citation: Zhirnik AS, Rodina AV, Semochkina YuP, Vysotskaya OV, Smirnova OD, Ratushnyak MG, Moskaleva EYu. Cognitive Disturbances and the State of Brain Glial Cells in Mice Exposed to Fractionated Whole-Brain Irradiation. Medical Radiology and Radiation Safety. 2022;67(5):10–17. (In Russian). DOI: 10.33266/1024-6177-2022-67-5-10-17

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Conflict of interest. The authors declare no conflict of interest.

Financing. Research Center Kurchatov Institute.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.06.2022. Accepted for publication: 25.08.2022.