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