Abstract
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.
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References
Richter-Levin, G., Acute and Long-Term Behavioral Correlates of Underwater Trauma-Potential Relevance to Stress and Post-Stress Syndromes, Psychiatry Res., 1988, vol. 79, no. 1, pp. 73–83.
Yehuda, R., Post-Traumatic Stress Disorder, N. Engl. J. Med., 2002, vol. 346, no. 2, pp. 108–114.
Giap, B., Jong, C., Ricker, G., et al., The Hippocampus: Anatomy, Patophysiology and Regenerative Capasity, J. Head Trauma Rehabilitation, 2000, vol. 15, no. 3, pp. 875–879.
Vaido, A.I., Physiological-Genetic Analysis of the Nervous System Excitability and Behavior in Laboratory Rats, Extended Abstract of Doctoral (Biol.) Dissertation, St. Petersburg, 2000, p. 34.
Shiryaeva, N.V., Vaido, A.I., and Lopatina, N.G., The Effect of Neurotization after a Long Period Following Its Termination on the Behavior of Rats Differing by Nervous System Excitability, Pavlov J. Higher Nerv. Act., 1996, vol. 46, no. 1, pp. 157–162.
Ordyan, N.E., Vaido, A.I., Rakitskaya, V.V., et al., Functioning of Hypophysial Adrenocortical System in Rats Selected by the Threshold of Sensitivity to Electrical Current, Byull. Eksp. Biol. Med., 1998, vol. 125, no. 4, pp. 443–445.
Hecht, K., Treptov, K., Choinovski, K., et al., Die raumzeitliche Organisation der Reiz-Reaktion-Beziehungen bedingtreflektorischer Prozesse, Yena: Fischer, 1972.
Sumner, T.A., A Simple Technique for Demonstrating Centromeric Heterochromatin, Exp. Cell. Res., 1972, vol. 75, pp. 304–306.
Dyuzhikova, N.A., Vaido, A.I., Lopatina, N.G., et al., Effect of Prenatal Emotional-Pain Stress on the Status of Interphase Chromatin in Neurons of the Rat Developing Brain with Various Excitation of the Nervous System, Tsitologiya, 2000, vol. 42, no. 8, pp. 772–786.
Sapolsky, R.M., Atrophy of Hippocampus in Posttraumatic Stress Disorder: How and When, Hippocampus, 2001, vol. 11, pp. 90–91.
Uno, H., Tarara, R., Else, J.G., et al., Hippocampus Damage Associated with Prolonged and Fatal Stress in Primates, J. Neurosci., 1989, vol. 9, no. 5, pp. 1705–1711.
Mizoguchi, K., Kanishita, T., Chui, D.H., et al., Stress Induces Neuronal Death in the Hippocampus of Rats, Neurosci. Lett., 1992, vol. 138, no. 1, pp. 157–160.
Volmann-Hondorf, G.K., Flugge, G., and Fuchs, E., Chronic Psychosocial Stress Does not Affect the Number of Pyramidal Neurons in Tree Shrew Hippocampus, Neurosci. Lett., 1997, vol. 223, nos. 2–3, pp. 121–124.
Bremner, J.D., Hypotheses and Controversies to Effects of Stress on Hippocampus: An Arrangement for Stress-Induced Damage of the Hippocampus in Patient with Posttraumatic Stress Disorder, Hippocampus, 2001, vol. 11, no. 2, pp. 85–89.
Stam, R., Bruijnzeel, A.W., and Wiegant, V.M., Long-Lasting Stress Sensitization, Eur. J. Pharmacol., 2000, vol. 405, nos. 1–3, pp. 217–240.
Irvin, L.N., Gene Expression in the Hippocampus of Behaviorally Stimulated Rats: Analysis by DNA Microarray, Brain Res. Mol. Brain Res., 2001, vol. 96, nos. 1–2, pp. 163–169.
Levenson, J.M. and Sweatt, J.D., Epigenetic Mechanisms in Memory Formation, Nat. Rev. Neurosci., 2006, vol. 281, no. 23, pp. 15763–15773.
Kulikova, O.G., Reikhart, B.A., and Sapronov, N.S., Involvement of the Genetic Apparatus in Memory Formation Mechanisms: The Role of the Neuronal Calcium- Regulatory System in Rats, Pavlov J. Higher Nerv. Act., 1997, vol. 47, no. 4, pp. 708–713.
Jung, B.P., Zhang, G., Ho, W., et al., L. Transient Forebrain Ischemia Alters the mRNA Expression of Methyl DNA-Binding Factors in the Adult Rat Hippocampus, Neuroscience, 2002, vol. 115, no. 2, pp. 515–524.
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Original Russian Text © A.I. Viado, N.A. Dyuzhikova, N.V. Shiryaeva, N.E. Sokolova, V.V. Vshivtseva, Yu.N. Sawenko, 2009, published in Genetika, 2009, Vol. 45, No. 3, pp. 342–348.
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Viado, A.I., Dyuzhikova, N.A., Shiryaeva, N.V. et al. Systemic control of the molecular, cell, and epigenetic mechanisms of long-lasting consequences of stress. Russ J Genet 45, 298–303 (2009). https://doi.org/10.1134/S1022795409030065
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DOI: https://doi.org/10.1134/S1022795409030065