P.1.a.016 Emotionally painful stress causes changes in L1 insertion pattern in the hippocampus in rats with different nervous system excitability

Stress can induce structural changes in the brain and contribute to a variety of chronic diseases from post-traumatic stress disorder to depression. The hippocampus is a highly plastic brain region particularly susceptible to the effects of environmental stress. A genomic stress response partly consists in changes in insertion activity of transposable elements. Retrotransposons account for ~45% of the mammalian genome. Mechanisms of action of stress and the formation of posttraumatic stress disorder (PTSD) in human are associated with retrotransposons (LINE1, L1) activity in various tissues. Endogenous retrotransposition of L1 elements has been proposed as one potential mechanism generating neuronal genome diversity. They are capable of inserting into new genomic locations, which can result in deleterious outcomes. The greatest interest is the study of these processes in the brain due to individual variability of neural processes to effective pharmacotherapy path finding. The purpose of this work was to investigate the effect of stress on the LINE1 insertion pattern in the hippocampus. We used the model of emotional stress for the PTSD-like state formation in two lines of rats with genetically determined differences in the level of excitability of the nervous system (low and high) to study of emotionally painful stress (3 types: short-term, long-term and massive stress) effect on LINE1 retrotransposon insertion polymorphism in the dentate gyrus of the hippocampus. L1 insertions in the promoter of gene GRIN1 [glutamate receptor ionotropic N-methyl-D-aspartate (NMDA) subtype, subunit 1] examined by two-step PCR (general and directed). Glutamate NMDA receptors play a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. These receptors mediate neuronal functions in glutamate neurotransmission. NMDAR-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stressrelated disorders. NMDA receptor subunit 1 is a core molecule in the NMDA receptor complex. GRIN1 expression is associated with neurotransmission efficiency and state of the nervous system. We suppose that L1 retrotransposon insertions to promoter of GRIN1 gene will alter GRIN1 expression. It was shown that L1 insertion pattern depends on the level of excitability of the nervous system, intensity and duration of stress exposure. The most variable spectrum of L1 transposable elements activity (L1 insertion pattern) is detected under the influence of massive stress in the rats with low excitability of the nervous system. We assume that L1 retrotransposon insertions take part in the regulation of expression of candidate genes associated with the stress response and the formation of psychopathology. P.1.a.017 Genetic variants in kinesin family member 13A (KIF13A) affect susceptibility to schizophrenia in Korean population