Skip to main content
SpringerLink
Log in

Effect of dexamethasone on the expression of immediate early genes c-fos and c-jun in different regions of the neonatal brain

  • Genomics. Transcriptomics
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

The ratio of the expression levels of the immediate early genes c-jun and c-fos that encode components of the AP-1 transcription complex determines the direction of changes in the expression of genes controlled by the complex, including changes induced by glucocorticoids. The aim of the present work was to assess the levels of mRNA encoded by genes c-jun and c-fos and the ratio of expression levels of these genes in various regions of the neonatal rat brain after the administration of dexamethasone, a selective ligand of the glucocorticoid receptor. The level of mRNA encoded by the immediate early gene c-fos in the hippocampus and prefrontal cortex of 3-day-old rat pups was elevated at 30, 60, and 120 min after dexamethasone administration. The basal level of c-fos gene expression in the brainstem was higher than in the cortex and hippocampus, and administration of the hormone was followed by a reduction in the amount of transcript detectable in the brainstem after 2 h. As a result, the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats was doubled after dexamethasone administration. The dexamethasone-induced shift of the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats towards a predominance of c-jun reported for the first time in the present work may induce the expression of genes that contain AP-1 response elements in the promoters, since the glucocorticoid receptor can be involved in protein–protein interactions with the Jun/Jun homodimer of the AP-1 complex.

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

Similar content being viewed by others

Abbreviations

GR:

glucocorticoid receptor

References

  1. Turpaev K.T. 2006. Role of transcription factor AP-1 in integration of cell signaling systems. Mol. Biol. (Moscow). 40 (6), 851–866.

    Article  CAS  Google Scholar 

  2. Kassel O., Herrlich P. 2007. Crosstalk between the glucocorticoid receptor and other transcription factors: molecular aspects. Mol. Cell Endocrinol. 275, 13–29.

    Article  CAS  PubMed  Google Scholar 

  3. Rani C.S., Elango N., Wang S.S., Kobayashi K., Strong R. 2009. Identification of an activator protein-1-like sequence as the glucocorticoid response element in the rat tyrosine hydroxylase gene. Mol. Pharmacol. 75, 589–598.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kalinina T.S., Shishkina G.T., Dygalo N.N. 2012. Induction of tyrosine hydroxylase gene expression by glucocorticoids in the perinatal rat brain is age-dependent. Neurochem. Res. 37, 811–818.

    Article  CAS  PubMed  Google Scholar 

  5. Teurich S., Angel P. 1995. The glucocorticoid receptor synergizes with Jun homodimers to activate AP-1-regulated promoters lacking GR binding sites. Chem. Senses. 20, 251–255.

    Article  CAS  PubMed  Google Scholar 

  6. Hoffman G.E., Smith M.S., Verbalis J.G. 1993. c-Fos and related immediate early gene products as markers of activity in neuroendocrine systems. Front. Neuroendocrinol. 14, 173–213.

    Article  CAS  PubMed  Google Scholar 

  7. Healy S., Khan P., Davie J.R. 2013. Immediate early response genes and cell transformation. Pharmacol. Ther. 137, 64–77.

    Article  CAS  PubMed  Google Scholar 

  8. Kalinina T.S., Bannova A.V., Dygalo N.N. 2001. Content of apoptotic enzyme caspase-3 mRNA in brain stem and cortex in rats during postnatal ontogeny. Bull. Exp. Biol. Med. 132, 748–750.

    Article  CAS  PubMed  Google Scholar 

  9. Bannova A.V., Menshanov P.N., Ilinykh F.A., Kalinina T.S., Dygalo N.N. 2005. Bax and Bcl-XL apoptosis protein mRNA in rat brain stem and cortex during ontogeny. Bull. Exp. Biol. Med. 139, 700–702.

    Article  CAS  PubMed  Google Scholar 

  10. Buss R.R., Sun W., Oppenheim R.W. 2006. Adaptive roles of programmed cell death during nervous system development. Annu. Rev. Neurosci. 29, 1–35.

    Article  CAS  PubMed  Google Scholar 

  11. Moisiadis V.G., Matthews S.G. 2014. Glucocorticoids and fetal programming: 1. Outcomes. Nat. Rev. Endocrinol. 10, 391–402.

    Article  CAS  PubMed  Google Scholar 

  12. Slotkin T.A., Kreider M.L., Tate C.A., Seidler F.J. 2006. Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems. Neuropsychopharmacology. 31, 904–911.

    Article  CAS  PubMed  Google Scholar 

  13. Chomczynski P., Sacchi N. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction. Anal. Biochem. 162, 156–159.

    Article  CAS  PubMed  Google Scholar 

  14. Parma D.L., Benasayag S.J., Szijan I. 1991. Expression of c-myc and c-fos oncogenes in different rat brain regions during postnatal development. Int. J. Dev. Neurosci. 9, 613–619.

    Article  CAS  PubMed  Google Scholar 

  15. Salehi M., Barron M., Merry B.J., Goyns M.H. 1999. Fluorescence in situ hybridization analysis of the fos/jun ratio in the ageing brain. Mech. Ageing Dev. 107, 61–71.

    Article  CAS  PubMed  Google Scholar 

  16. Olesen K.M., Auger A.P. 2005. Sex differences in Fos protein expression in the neonatal rat brain. J. Neuroendocrinol. 17, 255–261.

    Article  CAS  PubMed  Google Scholar 

  17. Dygalo N.N, Kalinina T.S, Shishkina G.T. 2008. Neonatal programming of rat behavior by downregulation of alpha2A-adrenoreceptor gene expression in the brain. Ann. NY Acad. Sci. 1148, 409–414.

    Article  PubMed  Google Scholar 

  18. O’Donnell A., Odrowaz Z., Sharrocks A.D. 2012. Immediate-early gene activation by the MAPK pathways: What do and don’t we know? Biochem. Soc. Trans. 40, 58–66.

    Google Scholar 

  19. Slotkin T.A., Zhang J., McCook E.C., Seidler F.J. 1998. Glucocorticoid administration alters nuclear transcription factors in fetal rat brain: Implications for the use of antenatal steroids. Brain Res. Dev. Brain Res. 111, 11–24.

    Article  CAS  PubMed  Google Scholar 

  20. Szakács R., Fazekas I., Mihály A., Krisztin-Péva B., Juhász A., Janka Z. 2010. Single-dose and chronic corticosterone treatment alters c-Fos or FosB immunoreactivity in the rat cerebral cortex. Acta. Histochem. 112, 147–160.

    Article  PubMed  Google Scholar 

  21. Brown E.R., Sawchenko P.E. 1997. Hypophysiotropic CRF neurons display a sustained immediate-early gene response to chronic stress but not to adrenalectomy. J. Neuroendocrinol. 9, 307–316.

    Article  CAS  PubMed  Google Scholar 

  22. Hansson A.C., Fuxe K. 2008. Time-course of immediate early gene expression in hippocampal subregions of adrenalectomized rats after acute corticosterone challenge. Brain Res. 1215, 1–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Skórzewska A., Bidzinski A., Lehner M., Turzynska D., Wislowska-Stanek A., Sobolewska A., Szyndler J., Maciejak P., Taracha E., Plaznik A. 2006. The effects of acute and chronic administration of corticosterone on rat behavior in two models of fear responses, plasma corticosterone concentration, and c-Fos expression in the brain structures. Pharmacol. Biochem. Behav. 85, 522–534.

    Article  PubMed  Google Scholar 

  24. Karst H., Joëls M. 2005. Corticosterone slowly enhances miniature excitatory postsynaptic current amplitude in mice CA1 hippocampal cells. J. Neurophysiol. 94, 3479–3486.

    Article  CAS  PubMed  Google Scholar 

  25. van Hasselt F.N., de Visser L., Tieskens J.M., Cornelisse S., Baars A.M., Lavrijsen M., Krugers H.J., van den Bos R., Joëls M. 2012. Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats. PLoS ONE. 7, e37820.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kassel O., Sancono A., Kratzschmar J., Kreft B., Stassen M., Cato A.C. 2001. Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1. EMBO J. 20, 7108–7116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Biddie S.C, John S., Sabo P.J., Thurman R.E., Johnson T.A., Schiltz R.L., Miranda T.B., Sung M.H., Trump S., Lightman S.L., Vinson C., Stamatoyannopoulos J.A., Hager G.L. 2011. Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding. Mol. Cell. 43, 145–155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wei P., Inamdar N., Vedeckis W.V. 1998. Transrepression of c-jun gene expression by the glucocorticoid receptor requires both AP-1 sites in the c-jun promoter. Mol. Endocrinol. 12, 1322–1333.

    Article  CAS  PubMed  Google Scholar 

  29. Speksnijder N., Christensen K.V., Didriksen M., De Kloet E.R., Datson N.A. 2012. Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the expression of c-JUN in a neuronal context. J. Mol. Neurosci. 48, 209–218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Briski K.P., DiPasquale B.M., Gillen E. 1997. Induction of immediate-early gene expression in preoptic and hypothalamic neurons by the glucocorticoid receptor agonist, dexamethasone. Brain Res. 768, 185–196.

    Article  CAS  PubMed  Google Scholar 

  31. Kovács K.J. 2008. Measurement of immediate-early gene activation: c-fos and beyond. J. Neuroendocrinol. 20, 665–672.

    Article  PubMed  Google Scholar 

  32. Shah K., Tyagi S. 2013. Barriers to transmission of transcriptional noise in a c-fos c-jun pathway. Mol. Syst. Biol. 9, 687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia

    E. V. Sukhareva, N. N. Dygalo & T. S. Kalinina

  2. Novosibirsk State University, Novosibirsk, 630090, Russia

    N. N. Dygalo & T. S. Kalinina

Authors
  1. E. V. Sukhareva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. N. Dygalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. S. Kalinina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. V. Sukhareva.

Additional information

Original Russian Text © E.V. Sukhareva, N.N. Dygalo, T.S. Kalinina, 2016, published in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 2, pp. 266–271.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sukhareva, E.V., Dygalo, N.N. & Kalinina, T.S. Effect of dexamethasone on the expression of immediate early genes c-fos and c-jun in different regions of the neonatal brain. Mol Biol 50, 230–235 (2016). https://doi.org/10.1134/S0026893316020254

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893316020254

Keywords

Search

Navigation