Accepted_test

The study aims to identify new mechanisms underlying epileptogenesis. One approach to creating mouse models of epilepsy is chemical mutagenesis using N-ethyl-N-nitrosourea (ENU). Using this method, mouse mutants with impaired structure and function of the cerebral cortex were generated. We selected mutants with an increased susceptibility to epileptic seizures using the Krushinsky technique, which considers the degree of manifestation of audiogenic seizures. These animals with an epileptic phenotype were used to consolidate the mutation according to the developed crossing scheme. Thus, a new line of Soc mice (Socrates, formerly S8-3) with pronounced epileptiform activity was created. The resulting Socrates mutant line was characterized using molecular biology techniques, bioinformatics, statistical analysis, and basic behavioral phenotyping. The use of molecular genetic methods to develop a panel of SNPs made it possible to map DNA regions to identify target genes involved in the formation of epilepsy. Subsequent analysis of target genes showed changes in the expression of these genes. Studies using behavioral tests to describe the phenotype of these mutant mice have shown that individuals of the Soc line have reduced motor activity and learning ability, and at the same time increased orientation-exploratory activity, which correlates with their increased excitability. We also demonstrated that the Soc mutation is accompanied by an imbalance of excitation-inhibition, which is the main cause of the formation of epileptic events in the brain: a statistically significant increase in the number of interneurons and astrocytes was recorded in the cerebral cortex, dentate gyrus, and CA1 hippocampus.