Fragments of Oxidized Extracellular DNA Affect the Development of Oxidative Stress in the Peripheral Blood Mononuclear Cells in vitro in Patients with Childhood Autism

Abstract

Background: the etiology and pathogenesis of childhood autism (CA) is one of the important unresolved problems of child psychiatry. It has been shown that the concentration of extracellular DNA (cfDNA) in the blood significantly increases in children with CA, and to the greatest extent in patients with severe CA. Patients with more severe CA also have significantly elevated levels of the oxidized DNA marker 8-OHdG in cfDNA and nuclear DNA samples and the double-strand break marker γH2AX. The aim was to study the effect of oxidized cfDNA fragments on the formation of free radicals, oxidation and breaks of nuclear DNA in the peripheral blood mononuclear cells in vitro in children with CA. Patients and methods: the study involved 13 patients diagnosed with F84.02 according to ICD-10 and 10 conditionally healthy children as a control group. Clinical-psychopathological, molecularbiological, statistical methods were used. Results: oxidized model DNA fragments affect the peripheral blood mononuclear cells of children with CA and conditionally healthy donors in different ways. In the mononuclear cells of conditionally healthy donors, in response to exposure to oxidized DNA fragments, the levels of ROS (reactive oxygen species) (p < 0.05), DNA oxidation (p < 0.05) and chromosome damage (p < 0.05) increase, but within the next 24 hours these indicators return to the previous level. At the same time, in the mononuclear cells of children with CA, the levels of ROS, DNA oxidation, and chromosome damage also increase, but the subsequent decrease occurs more slowly, and the levels of these indicators do not return to their previous values. Conclusion: on the basis of the obtained results, it is possible to put forward a hypothesis about the participation of fragments of oxidized extracellular DNA in the pathogenesis of CA.