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Effectiveness of the DNA Double-Strand Breaks Repair System in Lymphocytes of Patients with Cognitive Impairments and Healthy Volunteers

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Abstract—

The individual differences in the efficiency of the DNA DSB repair have been evaluated in lymphocytes of patients with amnestic mild cognitive impairment (AMCI) and Alzheimer’s disease (AD) and of healthy volunteers by the level of residual γH2AX foci after γ-irradiation at a dose of 2 Gy. Lymphocytes isolated from the peripheral blood of the examined patients were frozen in a cell freezing medium. Before the study, the frozen lymphocytes were thawed, suspended in the RPMI 1640 medium supplemented with 10% inactivated fetal bovine serum, and subdivided into two halves. One half was γ-irradiated using a 60Co source on a GUT-200M facility at a dose of 2 Gy (a dose rate of 0.75 Gy/min) at 4°C. Control and irradiated lymphocytes were then cultured for 24 h, collected, fixed, and stored until the study of the number of spontaneous and residual foci of γH2AX performed using fluorescent microscopy after staining with fluorescent labeled antibodies. An increased number of residual γH2AX foci in lymphocytes as well as an increased number of lymphocytes containing such foci were found in AMCI and АD patients as compared with healthy volunteers. This suggests a decrease in the ability of the DNA DSB repair in these patients. Parameters of the cellular immunity and the serum concentration of TNF-α in the group of examined patients were normal. In the group of patients with the cognitive impairments (AMCI + AD), a correlation was found between the number of residual foci of γH2AX and the number of CD3+CD4+ lymphocytes and the concentration of proinflammatory cytokine TNF-α in the serum. This suggests the development of more pronounced neuroinflammation in patients with reduced ability to repair DNA DSB in this pathology.

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REFERENCES

  1. Gavrilova, S.I., Consilium medicum, 2005, vol. 7, no. 2, pp. 153–157.

  2. Jacobsen, E., Beach, T., Shen, Y., Li, R., and Chang, Y., Brain Res. Mol. Brain Res., 2004, vol. 128, no. 1, pp. 1–7. https://doi.org/10.1016/j.molbrainres.2004.05.023

    Article  CAS  PubMed  Google Scholar 

  3. Shanbhag, N.M., Evans, M.D., Mao, W., Nana, A.L., Seeley, W.W., Adame, A., Rissman, R.A., Masliah, E., and Mucke, L., Acta Neuropathol. Commun., 2019, vol. 7, no. 1, 77. https://doi.org/10.1186/s40478-019-0723-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tse, K.H., Cheng, A., Ma, F., and Herrup, K., Alzheimers Dement., 2018, vol. 14, pp. 664–679. https://doi.org/10.1016/j.jalz.2017.11.010

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lovell, M.A., Gabbita, S.P., and Markesbery, W.R., J. Neurochem., 1999, vol. 72, pp. 771–776. https://doi.org/10.1046/j.1471-4159.1999.0720771.x

    Article  CAS  PubMed  Google Scholar 

  6. Lovell, M.A., Xie, C., and Markesbery, W.R., Brain Res., 2000, vol. 855, pp. 116–123. https://doi.org/10.1016/s0006-8993(99)02335-5

    Article  CAS  PubMed  Google Scholar 

  7. Siddiquia, M.S., Francoisa, M., Heckerc, J., Fauntd, J., Fenecha, M.F., and Leiferta, W.R., Mutat. Res. Gen. Tox. En., 2018, vols. 829–830, pp. 6–18. https://doi.org/10.1016/j.mrgentox.2018.03.001

  8. Moskaleva, E.Y., Semochkina, Y.P., Rodina, A.V., Chukalova, A.A., and Posypanova, G.A., Radiation Biology. Radioecology, 2017, vol. 57, no. 3, pp. 245–256. https://doi.org/10.7868/S0869803117030018

    Article  Google Scholar 

  9. Johansson, P., Muslimovic, A., Hultborn, R., Fernström, E., and Hammarsten, O., BioTechniques, 2011, vol. 51, pp. 185–189. https://doi.org/10.2144/000113738

    Article  CAS  PubMed  Google Scholar 

  10. Banáth, J.P., Klokov, D., MacPhail, S.H., Banuelos, C.A., and Olive, P.L., BMC Cancer, 2010, vol. 10, 4. https://doi.org/10.1186/1471-2407-10-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Taneja, N., Davis, M., Choy, J.S., Beckett, M.A., Singh, R., Kron, S.J., and Weichselbaum, R.R., J. Biol. Chem., 2004, vol. 279, no. 3, pp. 2273–2280. https://doi.org/10.1074/jbc.M310030200

    Article  CAS  PubMed  Google Scholar 

  12. Lovell, M.A. and Markesbery, W.R., Nucleic Acids Res., 2007, vol. 35, no. 22, pp. 7497–7504. https://doi.org/10.1093/nar/gkm821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ismail, I.H., Wadhra, T.I., and Hammarsten, O., Nucleic Acids Res., 2007, vol. 35, no. 5, e36. https://doi.org/10.1093/nar/gkl1169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sharma, P.M., Ponnaiya, B., Taveras, M., Shuryak, I., Turner, H., and Brenner, D.J., PLoS One, 2015, vol. 10, no. 3, e0121083. https://doi.org/10.1371/journal.pone.0121083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sedelnikova, O.A., Horikawa, I., Redon, C., Nakamura, A., Zimonjic, D.B., Popescu, N.C., and Bonner, W.M., Aging Cell, 2008, vol. 7, pp. 89–100. https://doi.org/10.1111/j.1474-9726.2007.00354.x

    Article  CAS  PubMed  Google Scholar 

  16. Malashenkova, I.K., Krynskiy, S.A., Hailov, N.A., Ogurtsov, D.P., Ponomareva, E.V., Gavrilova, S.I., and Didkovsky, N.A., Allergology and Immunology, 2018, vol. 19, no. 4, pp. 206–213.

    Google Scholar 

  17. Schmitz, A., Bayer, J., Dechamps, N., Goldin, L., and Thomas, G., Int. J. Radiat. Oncol. Biol. Phys., 2007, vol. 68, no. 4, pp. 1169–1177. https://doi.org/10.1016/j.ijrobp.2007.03.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sedger, L.M. and McDermott, M.F., Cytokine Growth Factor Rev., 2014, vol. 25, no. 4, pp. 453–472. https://doi.org/10.1016/j.cytogfr.2014.07.016

    Article  CAS  PubMed  Google Scholar 

  19. Bystrom, J., Clanchy, F.I., Taher, T.E., Mangat, P., Jawad, A.S., Williams, R.O., and Mageed, R.A., Cytokine, 2018, vol. 101, pp. 4–13. https://doi.org/10.1016/j.cyto.2016.09.001

    Article  CAS  PubMed  Google Scholar 

  20. Litvinova, L.S., Todosenko, N.M., Khaziakhmato-va, O.G., Malinina, I.P., and Yurova, K.A., Bulletin of Siberian Medicine, 2017, vol. 16, no. 4, pp. 207–219.

    Article  Google Scholar 

  21. Swardfager, W., Lanctot, K., Rothenburg, L., Wong, A., Cappell, J., and Herrmann, N., Biol. Psychiatry, 2010, vol. 68, pp. 930–941. https://doi.org/10.1016/j.biopsych.2010.06.012

    Article  CAS  PubMed  Google Scholar 

  22. Kim, Y.S., Lee, K.J., and Kim, H., Psychogeriatrics, 2017, vol. 17, pp. 224–230. https://doi.org/10.1111/psyg.12218

    Article  PubMed  Google Scholar 

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Funding

The work was carried out within the framework of the State Assignment of the NRC Kurchatov Institute.

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Authors and Affiliations

  1. National Research Center (NRC) Kurchatov Institute, pl. Akademika Kurchatova 1, 123182, Moscow, Russia

    Yu. P. Semochkina, E. Yu. Moskaleva, I. K. Malashenkova, S. A. Krynskiy, N. A. Hailov & D. P. Ogurtsov

  2. Mental Health Research Center, Kashirskoe shosse 34, 115522, Moscow, Russia

    E. V. Ponomareva & S. I. Gavrilova

Authors
  1. Yu. P. Semochkina
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  2. E. Yu. Moskaleva
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  3. I. K. Malashenkova
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  4. S. A. Krynskiy
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  5. N. A. Hailov
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  6. D. P. Ogurtsov
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  7. E. V. Ponomareva
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  8. S. I. Gavrilova
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Correspondence to E. Yu. Moskaleva.

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COMPLIANCE WITH ETHICAL STANDARDS

Before participation in this study, patients and their relatives were familiarized with the study protocol and signed a voluntary informed consent form. The study was approved by the Ethics Committee of the Mental Health Science Center.

CONFLICT OF INTERESTS

The authors declare that they have no conflicts of interest.

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Translated by A. Medvedev

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Semochkina, Y.P., Moskaleva, E.Y., Malashenkova, I.K. et al. Effectiveness of the DNA Double-Strand Breaks Repair System in Lymphocytes of Patients with Cognitive Impairments and Healthy Volunteers. Biochem. Moscow Suppl. Ser. B 15, 139–146 (2021). https://doi.org/10.1134/S1990750821020098

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  • DOI: https://doi.org/10.1134/S1990750821020098

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