Effect of Long-Term Stress on H3Ser10 Histone Phosphorylation in Neuronal Nuclei of the Sensorimotor Cortex and Midbrain Reticular Formation in Rats with Different Nervous System Excitability

Abstract

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.

Epigenetic Modifications, Alcoholic Brain and Potential Drug Targets

“…Similarly, in a more recent study chronic ethanol administration alone caused an increase in histone H3 ser10 and ser28 (H3S10 or S28) phosphorylation, and binge ethanol reduced their levels. This pattern of histone phosphorylation is also associated with differential induction of genes implicated in liver injury [76] .…”

“…For instance, acute alcohol exposure in rats, was found to result in increased phosphorylation of histone H3 at ser-10 and ser-28, which in turn leads to transient activation of p38 [76] . In another work, acute and rapid intraperitoneal administration of ethanol was found to promote site-specific histone H3 phosphorylation at Ser10 and Ser28 in rat liver in vivo [77] .…”