[Systemic control of the molecular, cell, and epigenetic mechanisms of long-lasting consequences of stress].
Based on M.E. Lobashev's views of the systemic control of genetic and cytogeneitc processes and a substantial effect of excitability on plastic changes in the central nervous system (CNS), the effect of prolonged emotional and pain stress (PEPS) on the molecular, cell, and epigenetic mechanisms of injury memory was studied in rat strains bred for a certain excitability of the nervous system. PEPS was for the first time found to cause long-lasting (2 months) morphological alterations of the CA3 region of the hippocampus and to modify the genome activity of its pyramidal neurons. The two phenomena were potentiated by a genetically determined low functional state of the CNS. The post-stress regulation of the genome function in hippocampal neurons was mediated by changes in heterochromatin conformation, activation of methyl-CpG-binding protein (MeCP2) synthesis, and subsequent changes in acetylation of histone H4. Genetically determined high excitability of the nervous system proved to be a risk factor that affects the specifics and time course of the observed molecular, cell, and genetic transformations of neurons. The results provide for a better understanding of the epigenetic mechanisms of injury memory, which forms a pathogenetic basis for posttraumatic stress disorder and other human psychogenic conditions characterized by a prolonged duration.
Baĭdo
A I
AI
Diuzhikova
N A
NA
Shiriaeva
N V
NV
Sokolova
N E
NE
Vshivtseva
V V
VV
Savenko
Iu N
IuN
D000107:Acetylation; D000818:Animals; D044127:Epigenesis, Genetic; D016678:Genome / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008568:Memory; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000235:genetics* / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
D006570:Heterochromatin; D006657:Histones; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2