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Analysis of Markers of Oxidative Damage of Neurons and Neuroinflammation in the Long-Term Period after Gamma Irradiation of a Mouse Head at Different Doses

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Abstract

Reactive oxygen species (ROS), which are formed under the action of ionizing radiation and inflammation factors, react with lipids and lead to the formation of toxic metabolites; one of the most active among them is 4-hydroxy-2-nonenal (4-HNE). It modifies cell proteins by lysine, histidine, and cysteine residues and disrupts their functions. The purpose of this research is to assess the number of neurons containing 4-HNE-modified proteins two months after γ-irradiation of the head at doses of 2, 8, and 20 Gy and determine the development of neuroinflammation at this period. Mouse brain cells were isolated by centrifugation through Percoll solution after brain tissue treatment with accutase. The number of neurons and neurons containing 4-HNE-modified proteins, as well as the number of cells of resting and activated microglia, were analyzed using flow cytometry; the level of expression of proinflammatory cytokine TNFα gene in the hippocampus was analyzed using RT-PCR. It is shown that 14.3 ± 2.3% of neurons in the brains of control mice contain 4-HNE-modified proteins. Their number increased to 23.1 ± 2.6 and 34.8 ± 4.9% (p < 0.05) two months after irradiation of the head of mice at doses of 8 and 20 Gy. An increase in the proportion of activated microglia in isolated brain cells and the level of TNFα gene expression in the hippocampus in this period indicates the development of neuroinflammation. Therefore, in addition to direct damage during irradiation, neurons are exposed to ROS and toxic metabolites of lipid peroxidation, which are formed both during irradiation and during neuroinflammation developing in the long-term period after radiation exposure. The results of this research make it possible to consider the increase in the amount of 4-HNE-modified proteins in neurons as a marker of oxidative damage to these brain cells.

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Authors and Affiliations

  1. National Research Center “Kurchatov Institute”, Moscow, Russia

    E. Yu. Moskaleva, A. V. Rodina, Yu. P. Semochkina & O. V. Vysotskaya

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  1. E. Yu. Moskaleva
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  2. A. V. Rodina
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  3. Yu. P. Semochkina
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  4. O. V. Vysotskaya
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Correspondence to E. Yu. Moskaleva.

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Statement on the welfare of animals. All the experiments with animals were performed in accordance with the requirements of the Ethical Committee of the National Research Center “Kurchatov Institute”.

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Translated by D. Zabolotny

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Moskaleva, E.Y., Rodina, A.V., Semochkina, Y.P. et al. Analysis of Markers of Oxidative Damage of Neurons and Neuroinflammation in the Long-Term Period after Gamma Irradiation of a Mouse Head at Different Doses. Biol Bull Russ Acad Sci 49, 2467–2474 (2022). https://doi.org/10.1134/S1062359022120159

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  • DOI: https://doi.org/10.1134/S1062359022120159

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