Priority data on specific effect of long-term mental and pain stress on the dynamics of H4 histone acetylation in the pyramidal neuron nuclei of the hippocampal CA3 field in rats selected by the nervous system excitability were obtained using a comparative genetic method. The congruency of long-term post-stress modification of H4 histone acetylation in neurons of rats with high threshold excitability and behavioral changes intrinsic of these rats suggest that increased acetylation of H4 histone together with changes in heterochromatin conformation play a triggering role in long-term modifications of genome expression underlying the pathogenesis of posttraumatic stress disorders and other psychogenias.

The effects of long-term mental and pain stress on H3Ser10 histone phosphorylation in neurons of the the sensorimotor corex and midbrain reticular formation were studied 24 h, 2 weeks, and 2 months after exposure of rats differing by the nervous system excitability. Rats with high excitability threshold exhibited higher basal level of H3Ser10 histone phosphorylation in the midbrain reticular formation neurons than rats with low excitability threshold. The sensorimotor cortical neurons of the two strains did not differ by this parameter. Stress led to a significant increase in the counts of immunopositive neuronal nuclei in rats with low excitability threshold: the parameter increased significantly in the sensorimotor cortex 24 h after exposure and normalized in 2 weeks after neurotization. In the midbrain reticular formation of this rat strain stress stimulated H3Ser10 histone phosphorylation after 24 h and after 2 weeks; the parameter normalized after neurotization in 2 months. Hence, genetically determined level of the nervous system excitability was essential for the basal level of neuron phosphorylation and for the time course of this process after long-term exposure to mental and pain stress, depending on the brain structure. A probable relationship between H3Ser10 histone phosphorylation process and liability to obsessive compulsive mental disorders in humans was discussed.

Long-term effects of chronic emotional and pain stress on histone H3 phosphorylation by serine 10 in hippocampal CA3 neurons were examined 24 h, 2 weeks, and 2 months after termination of the stress procedure in 2 rat strains differing by excitability of the nervous system. The low excitable rats with high threshold (HT) of excitability were characterized by a high baseline level of histone H3 phosphorylation in comparison with the high excitable rats with low threshold (LT) of excitability. The long-term emotional and pain stress significantly changed the number of positive immune cells in highly excitable rats: this parameter increased in 24 h and 2 weeks after the stress, but returned to the control level in 2 months. In contrast, stress did not affect histone H3 phosphorylation in low excitable rats. Thus, long-term (up to 2 weeks) changes in histone H3 phosphorylation were reveled in rat hippocampal CA3 neurons, which depended on genetically determined functional status of the nervous system.

In rats with low excitability threshold of the nervous system demonstrating significant and persistent behavioral disorders under stress conditions, the content of methylcytosine-binding protein MeCP2 in neuronal nuclei of hippocampal field CA3 decreased over 2 weeks after long-term emotional and pain stress. It was hypothesized that protein MeCP2 triggers epigenetic changes in DNA that underlie "stress memory".

We performed immunohistochemical analysis of the expression of caspases 3, 9 and bcl-2 protein in rat brain at various terms after administration of LD50 of sodium thiopental. Expression of the specified apoptosis markers was found in the sensorimotor cortex and hippocampus (dentate gyrus and CA2 region).