Post-traumatic stress disorder: molecular mechanisms of the intergenerational and transgenerational inheritance

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Post-traumatic stress disorder is a mental disorder that is closely associated with dysfunction of the hypothalamic-pituitary-adrenal axis, and for its development is required the experience of a traumatic event that causes negative emotions and memories that persist for quite a long time. The likelihood of development of post-traumatic stress disorder is influenced both environmental factors, and genetic and epigenetic characteristics of the body. In this case epigenetic modifications act as dynamic biomarkers (“nanotags”) of the impact of the environment on the genome (epigenome), which can, under certain conditions, disappear or remain not only in an individual directly exposed to psychogenic trauma, but also transmitted over a number of generations. Review focuses on the possible mechanisms of intergenerational and transgenerational inheritance of the biological effects of post-traumatic and stress-related disorders.

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作者简介

E. Patkin

Institute of Experimental Medicine

编辑信件的主要联系方式.
Email: elp44@mail.ru
俄罗斯联邦, St. Petersburg, 197022

I. Suchkova

Institute of Experimental Medicine

Email: irsuchkova@mail.ru
俄罗斯联邦, St. Petersburg, 197022

S. Tsikunov

Institute of Experimental Medicine

Email: secikunov@yandex.ru
俄罗斯联邦, St. Petersburg, 197022

H. Sofronov

Institute of Experimental Medicine; Military Medical Academy named after. C.M. Kirov of the Ministry of Defense of the Russian Federation

Email: gasofronov@mail.ru
俄罗斯联邦, St. Petersburg, 197022; St. Petersburg, 194044

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2. Fig. 1. Differences between intergenerational and transgenerational inheritance of biological effects caused by exposure to different natures. F0, F1, F2 and F3 – generations of individuals; 5mC/5hmC – DNA methylation and hydroxymethylation: stars inside circles and squares – gametes (spermatogonia/oogonia, spermatocytes/oocytes).

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3. Fig. 2. Putative molecular bases of the development of PTSD and stress-related disorders. 5mC/5hmC – DNA methylation and hydroxymethylation; epigen-R/gen-R – PTSD-resistant epigenotype/genotype; epigen-S/gen-S – PTSD-sensitive epigenotype/genotype (the presence of mutations and/or epimutations associated with the risk of developing PTSD and stress-related disorders); F0, F1, Fn – generations of individuals exposed to traumatic stress and/or inherited the biological effects of PTSD.

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4. Fig. 3. Scheme of putative molecular mechanisms of the influence of traumatic stress on the epigenome of germline cells (sex cells), responsible for intergenerational and transgenerational inheritance of its biological effects. DNMTs – DNA methyltransferases; TETs – proteins from the “ten-eleven translocation” family of methylcytosine dioxygenase (DNA demethylases); HATs – histone acetyltransferases; HMTs – histone methyltransferases; HDACs – histone deacetylases; HDMs – histone demethylases.

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