Acute and chronic stresses increase the level of oxidized cell-free DNA in plasma and hippocampus of rats - 11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Anton Filev ^1,2 Galina Shmarina ^2,3,5 Elizaveta Ershova ^1,2 Natalia Veiko ² Andrey Martynov ² Olga Dolgikh ² Maria Borzikova ^2,3 Anastasiya Poletkina ² Anastasiya Bekker ³ Zosim Volynshchikov ³ Svetlana Kostyuk ^1,2,3 Pavel Umriukhin ^3,4

¹V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia
²Laboratory of molecular biology, Research Centre for Medical Genetics, Moscow, Russia
³Department of normal physiology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
⁴Laboratory of systemic mechanisms of emotional stress, P.K. Anokhin institute of normal physiology, Moscow, Russia
⁵Cytokine laboratory, G.N. Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Russia

Alterations in plasma cell-free DNA (cfDNA) concentration has been described in various pathologies (cancer, trauma, stroke, myocardial infarction) and in physiological processes such as pregnancy and aging. All these conditions are associated with oxidative stress. It is known that in humans various psychological stress and physical stress induce DNA oxidation. However, no studies in experimental models to mimic acute, subacute and prolonged stress stimuli resulting in DNA oxidation, have been performed. The aim of the study was to assess the levels of oxidized cfDNA in blood plasma and hippocampus tissue of Wistar rats following exposure to various stressful stimuli. The rats were subjected to acute (2 h) stress, subchronic (2 days) stress and prolonged, induced by different stimuli during 11 days chronic stress. Oxidative modifications of cfDNA in plasma and hippocampus tissue were assessed by antibodies against 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG). cfDNA concentration (medians) in plasma of subchronic stress and prolonged chronic stress were 56.1±19.6 ng/ml and 40.4±24.3 ng/ml, both versus 10.4±2.0 in control rats ( (p=0.095 and p=0.049, respectively). In the same experiment, levels of 8-oxodG in plasma cfDNA were as follows: 201.6±60.2 AU (P=0.023), 159.9±90.2 AU (P=0.244), 526.0±215.4 AU (P<0.004) in acute stress, subchronic stress, prolonged chronic stress, respectively, versus 64.7±15.4 AU (no stress, control). Similarly, 8-oxodG content in hippocampus homogenates of rats increased to 3.17±0.14 AU following acute stress (p=0.019), 3.0±0.48 AU in subchronic stress (P>0,05) and 3.57±0.32 AU after chronic stress (p=0.011), all compared to control animals (2.67±0.11 AU). In conclusion, our data demonstrate that both acute and chronic stresses but not subchronic stress in rats resulted in enhanced oxidative modifications both in plasma cfDNA and hippocampus tissue. The study was supported by RFBR grant № 17-29-06017ofi_m.