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A Study of Mitochondrial DNA Copy Number and Heteroplasmy in Different Rat Brain Regions after Cranial Proton Impact

  • MOLECULAR RADIOBIOLOGY
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Abstract—

Studies, accumulated over recent years, indicate that mitochondria are, along with the nucleus, the most important target of radiation damage. The structural and functional disturbances induced by radiation in these organelles influence post-radiation development in a whole complex of effects at the cellular and whole organism level in animals and humans. This study is aimed at determining changes in the number of mitochondrial DNA (mtDNA) copies relative to nuclear DNA (nDNA) and identifying mutant copies of mtDNA in three brain regions (in the hippocampus, cortex, and cerebellum) of rats, at different times after cranial proton impact. Real-time PCR and a method of cleavage of mtDNA PCR amplicon heteroduplexes with Surveyor nuclease were used in this study. We revealed that after the proton exposure, the level of the mtDNA copy content in three brain regions of rats drastically increased with a simultaneous increase in the percentage of mutant mtDNA copies. The results obtained indicate that mtDNA synthesis and the level of its mutant copies differ in the hippocampus, cortex, and cerebellum of rats after cranial exposure to protons. One can suggest that increased mtDNA mutagenesis may result in mitochondrial dysfunction with oxidative stress induction, leading to nuclear genome instability and the development of delayed effects of ionizing radiation.

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Funding

This study is supported by the Russian Foundation for Basic Research, project no. 17-29-01007 ofi_m.

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia

    S. A. Abdullaev, E. V. Evdokimovskii & A. I. Gaziev

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  1. S. A. Abdullaev
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  2. E. V. Evdokimovskii
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  3. A. I. Gaziev
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Correspondence to S. A. Abdullaev.

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Conflict of interest. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Translated by A. Khaitin

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Abdullaev, S.A., Evdokimovskii, E.V. & Gaziev, A.I. A Study of Mitochondrial DNA Copy Number and Heteroplasmy in Different Rat Brain Regions after Cranial Proton Impact. Biol Bull Russ Acad Sci 47, 1489–1494 (2020). https://doi.org/10.1134/S1062359020110023

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  • DOI: https://doi.org/10.1134/S1062359020110023

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