Neurochemical Journal

, Volume 4, Issue 1, pp 35–40 | Cite as

Characteristics of the transcription factor HIF-1α expression in the rat brain during the development of a depressive state and the antidepressive effects of hypoxic preconditioning

  • K. A. BaranovaEmail author
  • V. I. Mironova
  • E. A. Rybnikova
  • M. O. Samoilov
Experimental Articles


The dynamics of HIF-1α expression during the development of stress-related depression, as well as after hypoxic preconditioning (HP), which has an antidepressant-like effect, were studied in the hippocampus, paraventricular hypothalamic nucleus, and neocortex of rats, using an immunocytochemical method. It has been found that the factor HIF-1α is induced in neurons in response to psychoemotional stress that causes the development of experimental depression in rats in the “learned helplessness” model. The profile of the stress-induced expression of HIF-1α in the hippocampus has a two-wave character: early expression on the first day and the delayed expression 10 days after the stress. No significant change was found in the neocortex. In the hypothalamus, up-regulation of HIF-1α expression was delayed (5–10 days). After HP by a moderate repetitive hypobaric hypoxia, which prevents the development of the depressive state in rats, the post-stress expression of HIF-1α was considerably altered in the brain regions studied. In the hippocampus of HP rats, the peak of the early expression lasted for about 5 days after the stress; we observed a multifold increase in its amplitude. In contrast, the HIF-1α delayed peak was eliminated. A similar but smaller effect of HP was also observed in the hypothalamus. The data obtained indicate that delayed HIF-1α expression in the hippocampus and hypothalamus was apparently involved in the mechanisms of pathogenesis of the depressive pathology. However, strong modifications in early and late post-stress expression of HIF-1α caused by HP obviously play an important role in increasing the brain’s tolerance to severe stresses and protection against the development of stress-induced depressive pathologies.

Key words

HIF-1α hypoxic preconditioning psychoemotional stress depressions neuroprotection “learned helplessness” 


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  1. 1.
    Semenza, G.L. and Wang, G.L., Mol. Cell. Biol., 1992, vol. 12, pp. 5447–5454.PubMedGoogle Scholar
  2. 2.
    Wang, G.L., Jiang, B.H., Rue, E.A., and Semenza, G.L., Proc. Natl. Acad. Sci. USA, 1995, vol. 92, pp. 5510–5514.CrossRefPubMedGoogle Scholar
  3. 3.
    Gu, Y.Z., Hogenesch, J.B., and Bradfield, C.A., Annu. Rev. Pharmacol. Toxicol, 2000, vol. 40, pp. 519–561.CrossRefPubMedGoogle Scholar
  4. 4.
    Huang, L.E., Gu, J., Schau, M., and Bunn, H.F., Proc. Natl. Acad. Sci. USA, 1998, vol. 95, pp. 7987–7992.CrossRefPubMedGoogle Scholar
  5. 5.
    Ivan, M., Kondo, K., Yang, H.F., et al., Science, 2001, vol. 292, pp. 464–468.CrossRefPubMedGoogle Scholar
  6. 6.
    Treins, C., Giorgetti-Peraldi, S., Murdaca, J. et al., Mol. Endocrinol., 2005, vol. 19, pp. 1304–1317.CrossRefPubMedGoogle Scholar
  7. 7.
    Peng, X.H., Karna, P., Cao, Z., et al., J. Biol. Chem., 2006, vol. 281, pp. 25903–25914.CrossRefPubMedGoogle Scholar
  8. 8.
    An, W.G., Kanekal, M., Simon, M.C., et al., Nature, 1998, vol. 392, pp. 405–408.CrossRefPubMedGoogle Scholar
  9. 9.
    Maxwell, P.H., Pugh, C.W., and Ratcliffe, P.J., Curr. Opin. Genet. Dev, 2001, vol. 11, pp. 293–299.CrossRefPubMedGoogle Scholar
  10. 10.
    Isaacs, J.S., Jung, Y.J., Mimnaugh, E.G., et al., J. Biol. Chem., 2002, vol. 277, pp. 29936–29944.CrossRefPubMedGoogle Scholar
  11. 11.
    Kim, H.L., Cassone, M., Otvos, L., and Vogiatzi, P., Cancer Biol. Ther, 2008, vol. 7, pp. 10–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Kim, W.Y., Oh, S.H., Woo, J.K., et al., Cancer Res., 2009, vol. 69, pp. 1624–1632.CrossRefPubMedGoogle Scholar
  13. 13.
    Richard, D.E., Berra, E., Gothie, E., et al., J. Biol. Chem., 1999, vol. 274, pp. 32631–32637.CrossRefPubMedGoogle Scholar
  14. 14.
    Yun, S.P., Lee, M.Y., Ryu, J.M., et al., Am. J. Physiol. Cell. Physiol, 2009, vol. 296, pp. 317–326.CrossRefGoogle Scholar
  15. 15.
    Kang, M.J., Jung, S.M., Kim, M.J., et al., FEBS J, 2008, vol. 275, pp. 5969–5981.CrossRefPubMedGoogle Scholar
  16. 16.
    Kimura, H., Ogura, T., Kurashima, Y., et al., Biochem. Biophys. Res. Commun., 2002, vol. 296, pp. 976–982.CrossRefPubMedGoogle Scholar
  17. 17.
    Liu, J., Narasimhan, P., Yu, F., and Chan, P.H., Stroke, 2005, vol. 36, pp. 1264–1269.CrossRefPubMedGoogle Scholar
  18. 18.
    Bell, E.L. and Chandel, N.S., Essays Biochem, 2007, vol. 43, pp. 17–27.CrossRefPubMedGoogle Scholar
  19. 19.
    Kodama, T., Shimizu, N., Yoshikawa, N., et al., J. Biol. Chem., 2003, vol. 278, pp. 33384–33391.CrossRefPubMedGoogle Scholar
  20. 20.
    Leonard, M.O., Godson, C., Brady, H.R., and Taylor, C.T., J. Immunol, 2005, vol. 174, pp. 2250–2257.PubMedGoogle Scholar
  21. 21.
    Risau, W., Nature, 1997, vol. 386, pp. 671–674.CrossRefPubMedGoogle Scholar
  22. 22.
    Wenger, R.H., FASEB J., 2002, vol. 16, pp. 1151–1162.CrossRefPubMedGoogle Scholar
  23. 23.
    Luk’yanova, L.D., Patogenez, 2008, no. 3, pp. 4–12.Google Scholar
  24. 24.
    Rybnikova, E.A., Khozhai, L.I., Tyul’kova, E.I, et al., Morfologiya, 2004, vol. 125, no. 2, pp. 10–15.Google Scholar
  25. 25.
    Rybnikova, E., Vataeva, L., Tyulkova, E., et al., Behav. Brain. Res, 2005, vol. 160, pp. 107–114.CrossRefPubMedGoogle Scholar
  26. 26.
    Rybnikova, E.A., Mironova, V.I., Pivina, S.G., et al., Dokl. Biol. Sci, 2006, vol. 411, pp. 431–433.CrossRefPubMedGoogle Scholar
  27. 27.
    Rybnikova, E., Mironova, V., Pivina, S., et al., Neurosci. Let., 2007, vol. 417, pp. 234–239.CrossRefGoogle Scholar
  28. 28.
    Rybnikova, E., Mironova, V., Pivina, S., et al., Psychoneuroendocrinology, 2007, vol. 32, pp. 813–823.CrossRefPubMedGoogle Scholar
  29. 29.
    Rybnikova, E.A., Mironova, V.I., Tyul’kova, E.I., and Samoilov, M.O., Zhurn. Vyssh. Nerv. Deyat., 2008, vol. 4, pp. 475–482.Google Scholar
  30. 30.
    Seligman, M.E. and Beagley, G., J. Comp. Physiol. Psychol., 1975, vol. 88, pp. 534–541.CrossRefPubMedGoogle Scholar
  31. 31.
    Samoilov, M.O., Rybnikova, E.A., Tyul’kova, E.I., et al., Dokl. Akad. Nauk, 2001, vol. 381, pp. 513–515 [Dokl. (Engl. Transl.), vol. 381, pp. 36–138].Google Scholar
  32. 32.
    Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, 2nd Ed., San Diego: Acad. Press, 1986.Google Scholar
  33. 33.
    Jacobson, L. and Sapolsky, R., Endocr. Rev, 1991, vol. 12, pp. 118–134.CrossRefPubMedGoogle Scholar
  34. 34.
    Kaskow, J.W., Baker, D., and Geracioti, T.D., Peptides, 2001, vol. 22, pp. 845–851.CrossRefGoogle Scholar
  35. 35.
    Lucca, G., Comim, C.M., Valvassori, S.S., et al., J. Psychiatr. Res, 2009, vol. 43, pp. 864–869.CrossRefPubMedGoogle Scholar
  36. 36.
    Tringali, G., Pozzoli, G., Lisi, L., and Navarra, P., Endocrinol., 2007, vol. 148, pp. 4711–4715.CrossRefGoogle Scholar
  37. 37.
    Jelkmann, W., Intern. Med, 2004, vol. 43, pp. 649–659.CrossRefPubMedGoogle Scholar
  38. 38.
    Marti, H.H., J. Exp. Biol, 2004, vol. 207, pp. 3233–3242.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  • K. A. Baranova
    • 1
    • 2
    Email author
  • V. I. Mironova
    • 1
  • E. A. Rybnikova
    • 1
  • M. O. Samoilov
    • 1
  1. 1.Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of PhysiologyRussian Academy of SciencesSt. PetersburgRussia
  2. 2.St. PetersburgRussia

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