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17β-Estradiol-Induced Regulation of the Novel 5-HT1A-Related Transcription Factors NUDR and Freud-1 in SH SY5Y Cells

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Abstract

Nuclear deformed epidermal autoregulatory factor-1 (NUDR/Deaf-1) and five prime repressor element under dual repression (Freud-1) are novel transcriptional regulators of the 5-HT1A receptor, a receptor that has been implicated in the pathophysiology of various psychiatric illnesses. The antidepressant effect of 17β-Estradiol (17βE2) is purported to involve the downregulation of this receptor. We investigated the possible role of NUDR and Freud-1 in 17βE2-induced downregulation of the 5-HT1A receptor in the neuroblastoma cell line SH SY5Y. Cells were treated with 10 nM of 17βE2 for 3 or 48 h, followed by a 24-h withdrawal period. Proteins were isolated and analyzed by western blotting. 17βE2 treatment increased NUDR immunoreactivity while Freud-1 and the 5-HT1A receptor showed significant decreases. Upon withdrawal of 17βE2, protein expression returned to control levels, except for NUDR, which remained significantly elevated in the 3-h treatment. Taken together, these data support a non-genomic downregulation of 5-HT1A receptor protein by 17βE2, which does not involve NUDR and Freud-1. Rather, changes in both transcription factors seem to be compensatory/homeostatic responses to changes in 5-HT1A receptor induced by 17βE2. These observations further highlight the importance of NUDR and Freud-1 in regulating 5-HT1A receptor expression.

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References

  • Albert PR, Lemonde S (2004) 5-HT1A receptors, gene repression, and depression: guilt by association. Neuroscientist 10:575–593

    Article  PubMed  CAS  Google Scholar 

  • Bang OY, Hong HS, Kim DH, Kim H, Boo JH, Huh K, Mook-Jung I (2004) Neuroprotective effect of genistein against beta amyloid-induced neurotoxicity. Neurobiol Dis 16:21–28

    Article  PubMed  CAS  Google Scholar 

  • Bethea CL, Lu NZ, Gundlah C, Streicher JM (2002) Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol 23:41–100

    Article  PubMed  CAS  Google Scholar 

  • Biedler JL, Roffler-Tarlov S, Schachner M, Freedman LS (1978) Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 38:3751–3757

    PubMed  CAS  Google Scholar 

  • Czesak M, Lemonde, Peterson EA, Rogaeva A, Albert PR (2006) Cell-specific repressor or enhancer activities of Deaf-1 at a serotonin 1A receptor gene polymorphism. J Neurosci 26:1864–1871

    Article  PubMed  CAS  Google Scholar 

  • David SP, Murthy NV, Rabiner EA, Munafo MR, Johnstone EC, Jacob R, Walton RT, Grasby PM (2005) A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J Neurosci 25:2586–2590

    Article  PubMed  CAS  Google Scholar 

  • Hadjighassem, Austin MC, Szewczyk B, Daigle M, Stockmeier CA, Albert PR (2009) Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression. Biol Psychiatry 66:214–222

    Article  PubMed  CAS  Google Scholar 

  • Hendricks T, Francis N, Fyodorov D, Deneris E (1999) The ETS domain factor Pet-1 is an early and precise marker of central 5-HT neurons and interacts with a conserved element in serotonergic genes. J Neurosci 19:10348–10356

    PubMed  CAS  Google Scholar 

  • Iyo AH, Kieran N, Chandran A, Albert PR, Wicks I, Bissette G, Austin MC (2009) Differential regulation of the serotonin 1 A transcriptional modulators five prime repressor element under dual repression-1 and nuclear-deformed epidermal autoregulatory factor by chronic stress. Neuroscience 163(4):1119–1127

    Google Scholar 

  • Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, Sequeira A, Kushwaha N, Morris SJ, Basak A, Ou XM, Albert PR (2003) Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 23:8788–8799

    PubMed  CAS  Google Scholar 

  • Lemonde S, Du L, Bakish D, Hrdina P, Albert PR (2004) Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response. Int J Neuropsychopharmacol 7:501–506

    Article  PubMed  CAS  Google Scholar 

  • Lopez JF, Liberzon I, Vazquez DM, Young EA, Watson SJ (1999) Serotonin 1A receptor messenger RNA regulation in the hippocampus after acute stress. Biol Psychiatry 45:934–937

    Article  PubMed  CAS  Google Scholar 

  • Malyala A, Kelly MJ, Ronnekleiv OK (2005) Estrogen modulation of hypothalamic neurons, activation of multiple signaling pathways and gene expression changes. Steroids 70:397–406

    Article  PubMed  CAS  Google Scholar 

  • Mize AL, Alper RH (2002) Rapid uncoupling of serotonin-1A receptors in rat hippocampus by 17beta-estradiol in vitro requires protein kinases A and C. Neuroendocrinology 76:339–347

    Article  PubMed  CAS  Google Scholar 

  • Mize AL, Poisner AM, Alper RH (2001) Estrogens act in rat hippocampus and frontal cortex to produce rapid, receptor-mediated decreases in serotonin 5-HT1A receptor functions. Neuroendocrinology 73:166–174

    Article  PubMed  CAS  Google Scholar 

  • Ou XM, Lemonde S, Jafar-Nejad H, Bown CD, Goto A, Rogaeva A, Albert PR (2003) Freud-1: a neuronal calcium-regulated repressor of the 5-HT1A receptor gene. J Neurosci 23:7415–7425

    PubMed  CAS  Google Scholar 

  • Picotto G, Vazquez G, Boland R (1999) 17-oestradiol increases intracellular Ca2+ concentration in rat enterocytes. Potential role of phospholipase C-dependent store-operated Ca2+ influx. Biochem J 339:71–77

    Article  PubMed  CAS  Google Scholar 

  • Qiu J, Bosch MA, Tobias SC, Grandy DK, Scanlan TS, Ronnekleiv OK, Kelly MJ (2003) Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C. J Neurosci 23:9529–9540

    PubMed  CAS  Google Scholar 

  • Rogaeva A, Albert PR (2007) The mental retardation gene CC2D1A/Freud-1 encodes a long isoform that binds conserved DNA elements to repress gene transcription. Eur J Neurosci 26:965–974

    Article  PubMed  Google Scholar 

  • Rogaeva A, Galaraga K, Albert PR (2007) The Freud-1/CC2D1A family: transcriptional regulators implicated in mental retardation. J Neurosci Res 85:2833–2838

    Article  PubMed  CAS  Google Scholar 

  • Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G (1998) Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci 18:7394–7401

    PubMed  CAS  Google Scholar 

  • Szewczyk B, Albert PR, Burns AM, Czesak M, Overholser JC, Jurjus GJ, Meltzer HY, Konick LC, Dieter L, Herbst N, May W, Rajkowska G, Stockmeier CA, Austin MC (2009) Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder. Int J Neuropsychopharmacol 12:155–168

    Article  PubMed  CAS  Google Scholar 

  • Young EA, Midgley AR, Carlson NE, Brown MB (2000) Alteration in the hypothalamic–pituitary–ovarian axis in depressed women. Arch Gen Psychiatry 57:1157–1162

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported with Grant Number 17701 from the National Center for Research Resources (NCRR) a component of the National Institutes of Health (NIH) and its contents are solely the responsibility of NCRR or NIH.

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None of the authors have conflict of interest.

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Authors and Affiliations

  1. Graduate Program in Neuroscience, School of Graduate Studies in the Health Sciences, University of Mississippi Medical Center, Jackson, MS, USA

    Samuel O. Adeosun

  2. Department of Psychiatry and Human Behavior and Center for Psychiatric Neuroscience, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216-4505, USA

    Samuel O. Adeosun, Mark C. Austin & Abiye H. Iyo

  3. Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA

    Samuel O. Adeosun

  4. Department of Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada

    Paul R. Albert

Authors
  1. Samuel O. Adeosun
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  2. Paul R. Albert
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  3. Mark C. Austin
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  4. Abiye H. Iyo
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Correspondence to Abiye H. Iyo.

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Adeosun, S.O., Albert, P.R., Austin, M.C. et al. 17β-Estradiol-Induced Regulation of the Novel 5-HT1A-Related Transcription Factors NUDR and Freud-1 in SH SY5Y Cells. Cell Mol Neurobiol 32, 517–521 (2012). https://doi.org/10.1007/s10571-012-9809-3

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  • DOI: https://doi.org/10.1007/s10571-012-9809-3

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