MorphologyMorphology1026-35432949-2556Eco-Vector10180110.34922/AE.2020.158.4.004Research ArticleEFFECT OF LONG-TERM EMOTIONALPAINFUL STRESS ON THE HISTONE H3 PHOSPHORYLATION IN THE MEDIAL PREFRONTAL CORTEX AND BASOLATERAL AMYGDALA OF RATS WITH GENETIC DIFFERENCES IN EXCITABILITY OF THE NERVOUS SYSTEMDyuzhikovaN. A.Laboratory of Higher Nervous Activity Geneticsdyuzhikova@infran.ruPavlovaM. B.Laboratory of Higher Nervous Activity Genetics-LevinaA. S.Laboratory of Higher Nervous Activity Genetics-KhlebaevaD. A.-A.Laboratory of Higher Nervous Activity Genetics-VaidoA. I.Laboratory of Higher Nervous Activity Genetics-I. P. Pavlov Institute of Physiology of the RAS151020201584-5273327022022Copyright © 2020, Dyuzhikova N.A., Pavlova M.B., Levina A.S., Khlebaeva D.A., Vaido A.I.2020Objective - to study the effect of the long-term emotional-painful stress on the level of histone H3 phosphorylation at Ser10 (phH3-Ser10) in the medial prefrontal cortex (mPC) and basolateral amygdala (BLA) in the rats of two strains characterized by different excitability of the nervous system in normal conditions and at various intervals (24 hours, 2 weeks, 2 months) after the long-term emotional-painful stress (LEPS). Material and methods. The immunoreactivity of mPC and BLA cells to phH3-Ser10 was studied using the immunohistochemical method. The objects of investigation were selected rat strains: НТ (high threshold, low excitability of the nervous system) and LT (low threshold, high excitability of the nervous system). A long-term (15 days) exposure to emotional-painful stress according to K. Hecht’s scheme was used. Results. Intact rats with low nervous excitability (HT strain - high threshold) demonstrated more high basal level of phH3Ser10 in BLA cells than rats with high excitability (LT strain - low threshold). No differences in basal level of phH3-Ser10 between two rat strains were found. The exposure to emotional- painful stress caused alterations in the level of phH3-Ser10 in rats from both strains. Increase of phH3-Ser10 level in the mPC was short-term (24h after LEPS) in LT rats and long-term (up to 2 months) in HT rats. The long-term (up to 2 months) increase of phH3-Ser10 level after stress in the BLA was discovered in LT rats only. Conclusions. Long-term changes in histone H3 phosphorylation, which have structural specificity and depend on genetically determined functional state of rats nervous system, were revealed.phosphorylationH3 histonestressexcitabilityratsфосфорилированиегистон Н3стрессвозбудимостькрысы[Вайдо А. И., Ширяева Н. В., Павлова М. Б. и др. Селектированные линии крыс с высоким и низким порогом возбудимости: модель для изучения дезадаптивных состояний, зависимых от уровня возбудимости нервной системы // Лабораторные животные для научных исследований. 2018. № 3. С. 12-23.doi: 10.29296/2618723X-201803-02][Chakravarty S., Pathak S. S., Maitra S. et al. Epigenetic Regulatory Mechanisms in Stress-Induced Behavior // Int. Rev. Neurobiol. 2014. Vol. 115. P. 117-154. doi: 10.1016/B978-012-801311-3.00004-4][Kouzarides T. Chromatin modifications and their function // Cell. 2007. Vol. 128, Iss. 4. P. 693-705. doi: 10.1016/j.cell.2007.02.005][Morello N., Plicato O., Piludu M. A. et al. Effects of Forced Swimming Stress on ERK and Histone H3 Phosphorylation in Limbic Areas of Roman High- and Low-Avoidance Rats // PLoS ONE 2017. Vol. 12, Iss. 1. P. e0170093. doi: 10.1371/journal. pone.0170093][Mori T., Wakabayashi T., Ogawa H. et al. Increased histone H3 phosphorylation in neurons in specific brain structures after induction of status epilepticus in mice // PLoS One. 2013. Vol. 8, Iss. 10. P. e77710. doi: 10.1371/journal.pone.0077710][Nowak S. J., Corces V. G. Phosphorylation of histone H3 correlates with transcriptionally active loci // Genes Dev. 2000. Vol. 14. P. 3003-3013. doi: 10.1101/gad.848800][Paxinos G., Watson C. The rat brain in stereotaxic coordinates - 6th edition // Academic Press. 2007. P. 456.][Prigent C., Dimitrov S. Phosphorylation of serine 10 in histone H3, what for? // J. Cell Sci. 2003. Vol. 116, Pt 18. P. 3677-3685. doi: 10.1242/jcs.00735][Rotllant D., Pastor-Ciurana J., Armario A. Stress-induced brain histone H3 phosphorylation: contribution of the intensity of stressors and length of exposure // J. Neurochem. 2013. Vol. 125, Iss. 4. P. 599-609. doi: 10.1111/jnc.12214.]