The Psychoemotional Stress-Induced Changes in the Abundance of SatIII (1q12) and Telomere Repeats, but Not Ribosomal DNA, in Human Leukocytes

Abstract

INTRODUCTION. As shown earlier, copy number variations (CNV) in the human satellite III (1q12) fragment (f-SatIII) and the telomere repeat (TR) reflects the cell’s response to oxidative stress. The contents of f-SatIII and TR in schizophrenic (SZ) patients were found to be lower than in healthy controls (HC) in previous studies. The major question of this study was: ‘What are the f-SatIII and TR CNV dynamic changes in human leukocytes, depending on psychoemotional stress?’ MATERIALS AND METHODS. We chose a model of psychoemotional stress experienced by second-year medical students during their exams. Blood samples were taken in stressful conditions (exams) and in a control non-stressful period. Biotinylated probes were used for f-SatIII, rDNA, and TR quantitation in leukocyte DNA by non-radioactive quantitative hybridization in SZ patients (n = 97), HC (n = 97), and medical students (n = 17, n = 42). A flow cytometry analysis was used for the oxidative stress marker (NOX4, 8-oxodG, and γH2AX) detection in the lymphocytes of the three groups. RESULTS. Oxidative stress markers increased significantly in the students’ lymphocytes during psychoemotional stress. The TR and f-SatIII, but not the rDNA, contents significantly changed in the DNA isolated from human blood leukocytes. After a restoration period (post-examinational vacations), the f-SatIII content decreased, and the TR content increased. Changes in the blood cells of students during examinational stress were similar to those in SZ patients during an exacerbation of the disease. CONCLUSIONS. Psychoemotional stress in students during exams triggers a universal mechanism of oxidative stress. The oxidative stress causes significant changes in the f-SatIII and TR contents, while the ribosomal repeat content remains stable. A hypothesis is proposed to explain the quantitative polymorphisms of f-SatIII and TR contents under transient (e.g., students’ exams) or chronic (in SZ patients) stress. The changes in the f-SatIII and TR copy numbers are non-specific events, irrespective of the source of stress. Thus, our findings suggest that the psychoemotional stress, common in SZ patients and healthy students during exams, but not in a schizophrenia-specific event, was responsible for the changes in the repeat contents that we observed earlier in SZ patients.

Mild cognitive impairment is associated with low copy number of ribosomal genes in the genomes of elderly people

“…Unlike TR, the rDNA CN determined by the hybridization method does not change under stress conditions ( Konkova et al, 2020 ; Umriukhin et al, 2022 ) and is the same in various brain structures ( Ershova et al, 2019 ). We believe that rDNA CN is a stable genetic trait that does not change during normal aging (except for the possible loss of hypermethylated copies).…”

“…Syntol (Moscow, Russia) performed the synthesis and biotin labeling of the oligo-probe. Calibration dependencies relating the signal intensity to the TR repeat content in DNA were published earlier ( Umriukhin et al, 2022 ).…”

Ribosomal, Satellite III (1q12) and Telomere Repeat Copy Number Variations in Cystic Fibrosis Patients Used as a Model of Permanent Stress and Survivability

“…The contents of f-SatIII and TR in human DNA are known to depend on the subject’s age and stress status [37, 40, 43]. In view of this, all patients were divided into five groups: CF(0-2): N=37, the age was from 0.21 to 2 years, the ‘severe’ genotype CFTR was detected in 97% of patients from this group; CF (3-16): N=54, the age from 3 to 16 years, the ‘severe’ genotype was detected in 98% of the patients; CF(d): N=92, the age from 17 to 40 years, the ‘severe’ genotype detected in 68% of the patients.…”

“…The cells with high counts of the repeat are unable to divide and do not respond to stress by developing an adaptive response. These cells die when the stress levels rise [18, 37–40]. Transcription of satellite is one of the eventual mechanisms leading to the amplification of this repeat in some cells of a senescent population [41, 42].…”

Combined Assay of rDNA and SatIII Copy Numbers as an Individual Profile of Stress Resistance, Longevity, Fertility and Disease Predisposition

“…Hence, affective exam stress triggered a universal mechanism of oxidative stress, provoking a splash of SatIII copy number dynamics, presumably due to the repeat expansion, while the ribosomal repeat content remained stable. After the release of the stress and the restoration period during the post-examinational vacations, the SatIII content normalized, presumably being reduced by a hypothetical reverse mechanism that counterbalances the satellite repeat expansion [ 90 ]. These findings became a validation of the “pendulum model” published earlier [ 85 ].…”