Skip to main content
SpringerLink
Log in

Peculiarities of DNA and Histone H3 Methylation in the Hippocampus and Neocortex of Rats Subjected to Pathological Treatments during the Prenatal Period

  • EXPERIMENTAL ARTICLES
  • Published:
Neurochemical Journal Aims and scope Submit manuscript

Abstract—Stress during pregnancy can cause the structural and functional changes in the fetal brain, which subsequently lead to the formation of various neuropsychiatric diseases, including attention deficit hyperactivity disorder, depression, schizophrenia, autism, and others. Among the stress factors that can lead to disorders of fetal development, prenatal hypoxic stress is especially important. Epigenetic mechanisms may play a key role in the development of brain disorders, which are caused by stressful effects of various nature. The aim of this work was to study the age-related characteristics of DNA methylation (meDNA) and histone H3 at lysines 4 (meН3К4) and 9 (meН3К9) in the cells of the rat hippocampus and neocortex that are the most sensitive brain structures after severe hypobaric hypoxia (180 mmHg, 3 h) or administration of a synthetic glucocorticoid dexamethasone (0.8 mg/kg), which models the stress response of the mother’s body, on the 14–16th day of prenatal ontogeny. Using immunohistochemistry we detected age-related modifications of the intensity of meDNA and meH3K9 (but not meH3K4) in control animals, namely a decrease in the level of meDNA and meH3K9 in 18-month-old rats compared to 3-month-old rats. Severe hypobaric hypoxia or administration of dexamethasone on the 14–16th day of prenatal ontogeny led to a prolonged (up to 18 month) increase in the level of meDNA in all the brain structures studied. We also observed a progressive decrease in the level of meH3K4, an activating modification of chromatin, in the hippocampus and neocortex of rats. However, the level of meH3K9, an inhibitory modification of chromatin, in animals that were subjected to adverse treatments during the prenatal period decreased to a lesser extent with age than in the control rats. These data indirectly reflect a decrease in the transcriptional activity of the genome of prenatally stressed animals, which may underlie long-term changes in their learning abilities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. van Os, J. and Selten, J.P., Br. J. Psychiatry, 1998, vol. 172, pp. 324–326.

    Article  CAS  PubMed  Google Scholar 

  2. Bergh, B.R. and Marcoen, A., Child Dev., 2004, vol. 75, no. 4, pp. 1085–1097.

    Article  PubMed  Google Scholar 

  3. Beversdorf, D.Q., Manning, S.E., Hillier, A., Anderson, S.L., Nordgren, R.E., Walters, S.E., Nagaraja, H.N., Cooley, W.C., Gaelic, S.E., and Bauman, M.L., J. Autism. Dev. Disord., 2005, vol. 35, no. 4, pp. 471–478.

    Article  CAS  PubMed  Google Scholar 

  4. Khashan, A.S., Abel, K.M., McNamee, R., Pedersen, M.G., Webb, R.T., Baker, P.N., Kenny, L.C., and Mortensen, P.B., Arch. Gen. Psychiatry, 2008, vol. 65, no. 2, pp. 146–52.

    Article  PubMed  Google Scholar 

  5. Van Calster, B., Smits, T., Van Huffel, S., and Lagae, L., Neuropsychopharmacology, 2008, vol. 33, no. 3, pp. 536–545.

    Article  PubMed  Google Scholar 

  6. Grizenko, N., Fortier, M.E., Zadorozny, C., Thakur, G., Schmitz, N., Duval, R., and Joober, R., J. Can. Acad. Child. Adolesc. Psychiatry, 2012, vol. 21, no. 1, pp. 9–15.

    PubMed  PubMed Central  Google Scholar 

  7. Graignic-Philippe, R., Dayan, J., Chokron, S., Jacquet, A.Y., and Tordjman, S., Neurosci. Biobehav. Rev., 2014, vol. 43, pp. 137–162.

    Article  CAS  PubMed  Google Scholar 

  8. de Boo, H.A. and Harding, J.E., Aust. N. Z. J. Obstet. Gynaecol., 2006, vol. 46, pp. 4–14.

    Article  PubMed  Google Scholar 

  9. Warner, M.J. and Ozanne, S.E., Biochem. J., 2010, vol. 427, pp. 333–347.

    Article  CAS  PubMed  Google Scholar 

  10. Langley-Evans, S.C. and McMullen, S., Med. Princ. Pract., 2010, vol. 19, pp. 87–98.

    Article  PubMed  Google Scholar 

  11. Barker, D.J., Osmond, C., Kajantie, E., and Eriksson, J.G., Ann. Hum. Biol., 2009, vol. 36, pp. 445–458.

    Article  PubMed  Google Scholar 

  12. Harris, A. and Seckl, J., Horm. Behav., 2011, vol. 59, pp. 279–289.

    Article  CAS  PubMed  Google Scholar 

  13. Gluckman, P.D., Hanson, M.A., Cooper, C., and Thornburg, K.L., N. Engl. J. Med., 2008, vol. 359, pp. 61–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gluckman, P.D. and Hanson, M.A., Science, 2004, vol. 305, pp. 1733–1736.

    Article  CAS  PubMed  Google Scholar 

  15. Gonzalez-Rodriguez, P.J., Xiong, F., Li, Y., Zhou, J., and Zhang, L., Neurobiol. Dis., 2014, vol. 65, pp. 172–179.

  16. Li, Y., Gonzalez, P., and Zhang, L., Prog. Neurobiol., 2012, vol. 98, pp. 145–165.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wilcoxon, J.S. and Redei, E.E., Horm. Behav., 2007, vol. 51, no. 3, pp. 321–327.

    Article  CAS  PubMed  Google Scholar 

  18. Salomon, S., Bejar, C., Schorer-Apelbaum, D., and Weinstock, M., J. Neuroendocrinol., 2011, vol. 23, no. 2, pp. 118–128.

    Article  CAS  PubMed  Google Scholar 

  19. Reynolds, R.M., Clin. Obstet. Gynecol., 2013, vol. 56, no. 3, pp. 602–609.

    Article  PubMed  Google Scholar 

  20. Crowther, C.A., Doyle, L.W., Haslam, R.R., Hiller, J.E., Harding, J.E., and Robinson, J.S.,N. Engl. J. Med., 2007, vol. 357, pp. 1179–1189.

    Article  CAS  PubMed  Google Scholar 

  21. French, N.P., Hagan, R., Evans, S.F., Mullan, A., and Newnham, J.P., Am. J. Obstet. Gynecol., 2004, vol. 190, pp. 588–595.

    Article  CAS  PubMed  Google Scholar 

  22. Braun, T., Challis, J.R., Newnham, J.P., and Sloboda, D.M., Endocr. Rev., 2013, vol. 34, pp. 885–916.

    Article  CAS  PubMed  Google Scholar 

  23. Moors, M., Bose, R., Johansson-Haque, K., Edoff, K., Okret, S., and Ceccatelli, S., Toxicol. Sci., 2012, vol. 125, pp. 488–495.

    Article  CAS  PubMed  Google Scholar 

  24. Sorrells, S.F., Munhoz, C.D., Manley, N.C., Yen, S., and Sapolsky, R.M., Neuroendocrinology, 2014, vol. 100, no. 2, pp. 129–140.

    Article  CAS  PubMed  Google Scholar 

  25. Stutchfield, P.R., Whitaker, R., Gliddon, A.E., Hobson, L., Kotecha, S., and Doull, I.J., Arch. Dis. Child. Fetal. Neonatal. Ed., 2013, vol. 98, no. 3, pp. 195–200.

    Article  Google Scholar 

  26. Vataeva, L.A., Tyul’kova, E.I., Alekhin, A.N., and Stratilov, V.A., Zhurnal Evolyutsionnoi Fiziologii i Biokhimii, 2018, vol. 54, no. 6, pp. 404–410.

  27. Bhutani, N., Burns, D.M., and Blau, H.M., Cell, 2011, vol. 146, pp. 866–872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Suganuma, T. and Workman, J.L., Annu. Rev. Biochem., 2011, pp. 473–499.

  29. Egger, G., Liang, G., Aparicio, A., and Jones, P.A., Nature, 2004, vol. 429, pp. 457–463.

    Article  CAS  PubMed  Google Scholar 

  30. Chen, M. and Zhang, L., Drug. Discov. Today, 2011, vol. 16, pp. 1007–1018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Concepcion, K.R. and Zhang, L., Drug. Discov. Today, 2018, vol. 23, no. 10, pp. 1718–1732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Oakley, R., Busada, T., and Cidlowski, J., FASEB J., 2018, vol. 32, no. 10.

  33. Jobe, E.M. and Zhao, X., Brain Plasticity, 2017, vol. 3, no. 1, pp. 5–26.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Freitag, M. and Selker, E.U., Curr. Opin. Genet. Dev., 2005, vol. 15, pp. 191–199.

    Article  CAS  PubMed  Google Scholar 

  35. Weber, M., Hellmann, I., Stadler, M.B., Ramos, L., Pääbo, S., Rebhan, M., and Schübeler, D., Nat. Genet., 2007, vol. 39, pp. 457–466.

    Article  CAS  PubMed  Google Scholar 

  36. Perez-Perri, J.I., Acevedo, J.M., and Wappner, P., Int. J. Mol. Sci., 2011, vol. 12, pp. 4705–4721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tyul’kova, E.I., Vetrovoi, O.V., Sarieva, K.V., Vataeva, L.A., and Glushchenko, T.S., Neurochem. J., 2017, vol. 11, no. 4, pp. 309–314.

    Article  Google Scholar 

  38. Tyul’kova, E.I., Vataeva, L.A., Vetrovoi, O.V., Sarieva, K.V., and Stratilov, V.A., Tsitologiya, 2019, vol. 61, no. 2, pp. 98–105.

    Article  Google Scholar 

  39. Stroev, S.A., Tyul’kova, E.I., Vataeva, L.A., Samoilov, M.O., and Pel’to-Khuikko, M.T., Neurochem. J., 2011, vol. 5, no. 3, pp. 200–204.

  40. Slotkin, T.A., Kreider, M.L., Tate, C.A., and Seidler, F.J., Neuropsychopharmacology, 2006, no. 5, pp. 904–911.

  41. Vilaca, Junior P.E.A., Teixeira, A.A.C., Wanderley-Teixeira, V., Moraes, E.F., Araujo, A.C.C., and Maia, C.S., Int. J. Morphol., 2008, vol. 26, no. 3, pp. 523–527.

    Google Scholar 

  42. Tyul’kova, E.I., Vataeva, L.A., Samoilov, M.O., and Otellin, V.A., Zhurnal Akusherstva i Zhenskikh Boleznei, 2010, vol. 59, no. 4, pp. 99–110.

  43. Tyul’kova, E.I., Vataeva, L.A., Vetrovoi, O.V., and Romanovskii, D.Yu., Zhurn. Evolyuts. Biokhim. i Fiziol.im.I.M. Sechenova, 2015, vol. 51, no. 2, pp. 115–121.

    Google Scholar 

  44. Tyul’kova, E.I., Vataeva, L.A., and Vetrovoi, O.V., Detskaya Meditsina Severo-Zapada, 2018, vol. 7, no. 1, pp. 319–320.

    Google Scholar 

  45. Barker, D.J., Mol. Med. Today, 1995, vol. 1, no. 9, pp. 418–423.

    Article  CAS  PubMed  Google Scholar 

  46. Nyirenda, M.J. and Seckl, J.R., Int. J. Mol. Med., 1998, vol. 2, no. 5, pp. 607–614.

    CAS  PubMed  Google Scholar 

  47. Dasgupta, C., Chen, M., Zhang, H., Yang, S., and Zhang, L., Hypertension, 2012, vol. 60, pp. 697–704.

    Article  CAS  PubMed  Google Scholar 

  48. Liu, X., Wang, C., Liu, W., Li, J., Li, C., Kou, X., Chen, J., Zhao, Y., Gao, H., Wang, H., Zhang, Y., Gao, Y., and Gao, S., Nature, 2016, vol. 537, pp. 558–562.

    Article  CAS  PubMed  Google Scholar 

  49. Sauvageot, C.M. and Stiles, C.D., Curr. Opin. Neurobiol., 2002, vol. 12, pp. 244–249.

    Article  CAS  PubMed  Google Scholar 

  50. Takizawa, T., Nakashima, K., Namihira, M., Ochiai, W., Uemura, A., Yanagisawa, M., Fujita, N., Nakao, M., and Taga, T., Dev. Cell, 2001, vol. 1, pp. 749–758.

    Article  CAS  PubMed  Google Scholar 

  51. Koslowski, M., Luxemburger, U., Tureci, O., and Sahin, U., Oncogene, 2011, vol. 30, pp. 876–882.

    Article  CAS  PubMed  Google Scholar 

  52. Walczak-Drzewiecka, A., Ratajewski, M., Pulaski, L., and Dastych, J., Biochem. Biophys. Res. Commun., 2010, vol. 391, pp. 1028–1032.

    Article  CAS  PubMed  Google Scholar 

  53. Watson, J.A., Watson, C.J., McCann, A., and Baugh, J., Epigenetics, 2010, vol. 5, no. 1, pp. 293–296.

    Article  CAS  PubMed  Google Scholar 

  54. Kirova, Yu.I., Patol. Fiziol. Eksp. Ter., 2012, vol. 56, no. 3, pp. 51–55.

    Google Scholar 

  55. Kodama, T., Shimizu, N., Yoshikawa, N., Makino, Y., Ouchida, R., Okamoto, K., Hisada, T., Nakamura, H., Morimoto, C., and Tanaka, H., J. Biol. Chem., 2003, vol. 278, no. 35, pp. 33384–33391.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Russian Foundation of Basic Research, project no. 17-04-01118.

Author information

Authors and Affiliations

  1. Pavlov Institute of Physiology, Russian Academy of Sciences, nab. Makarova 6, 199034, St. Petersburg, Russia

    E. I. Tyul’kova, V. A. Stratilov, V. S. Barysheva & O. V. Vetrovoy

  2. Herzen Russian State Pedagogical University, St. Petersburg, Russia

    L. A. Vataeva

  3. Department of Biochemistry, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia

    O. V. Vetrovoy

Authors
  1. E. I. Tyul’kova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. A. Vataeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. A. Stratilov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. S. Barysheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. O. V. Vetrovoy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. I. Tyul’kova.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.

Ethical approval. The experiments complied with the requirements of the Council Directives of the European Community (86/609/EEC) on the use of animals for experimental research. The experimental protocols were approved by the Commission for the humane treatment of animals of the Pavlov Institute of Physiology of the Russian Academy of Sciences.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tyul’kova, E.I., Vataeva, L.A., Stratilov, V.A. et al. Peculiarities of DNA and Histone H3 Methylation in the Hippocampus and Neocortex of Rats Subjected to Pathological Treatments during the Prenatal Period. Neurochem. J. 14, 64–72 (2020). https://doi.org/10.1134/S1819712420010195

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1819712420010195

Keywords:

Search

Navigation