Effectiveness of the DNA double-strand breaks repair system in lymphocytes of patients with cognitive impairments and healthy volunteers

Semochkina Yu.P.1, Moskaleva E.Yu.1 , Malashenkova I.K.1, Krynskiy S.A.1, Hailov N.A.1, Ogurtsov D.P.1, Ponomareva E.V.2, Gavrilova S.I.2

1. NRC Kurchatov Institute, Moscow, Russia
2. Mental Health Research Center, Moscow, Russia
Section: Clinical and Diagnostic Research
DOI: 10.18097/PBMC20206604345      PubMed Id: 32893818
Year: 2020  Volume: 66  Issue: 4  Pages: 345-352
The individual differences in the efficiency of DNA DSB repair were estimated by the level of residual γH2AX foci after γ-irradiation at a dose of 2 Gy, in lymphocytes of patients with amnestic mild cognitive impairment (AMCI) and Alzheimer's disease (AD) and of healthy volunteers. Lymphocytes were isolated from the peripheral blood of the examined patients and were frozen in a medium for freezing cells. Before the study, the lymphocytes were thawed, suspended in RPMI 1640 culture medium supplemented with 10% inactivated fetal bovine serum, and half of the cells were γ-irradiated at 4°C from a 60Co source on a GUT-200M facility at a dose of 2 Gy (a dose rate of 0.75 Gy/min). Control and irradiated lymphocytes were cultured for 24 h, collected, fixed, and stored until the study of the number of spontaneous and residual foci of γH2AX using fluorescent microscopy after staining with fluorescent labeled antibodies. In lymphocytes of patients with AMCI and AD a higher number of residual γH2AX foci in lymphocytes and the higher number of lymphocytes with foci were found compared with healthy volunteers. This indicates a decrease in the ability to repair DNA DSB in these patients. Indicators of cellular immunity and the concentration of TNF-α in the blood serum 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 blood serum. This suggests the development of stronger neuroinflammation in patients with reduced ability to repair DNA DSB in this pathology.
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Keywords: DNA double-strand breaks, γH2AX, DNA repair, amnestic mild cognitive impairment, lymphocytes

Semochkina, Yu. P., Moskaleva, E. Yu., Malashenkova, I. K., Krynskiy, S. A., Hailov, N. A., Ogurtsov, D. P., Ponomareva, E. V., Gavrilova, S. I. (2020). Effectiveness of the DNA double-strand breaks repair system in lymphocytes of patients with cognitive impairments and healthy volunteers. Biomeditsinskaya khimiya, 66(4), 345-352.
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