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Brain-derived neurotrophic factor uses CREB and Egr3 to regulate NMDA receptor levels in cortical neurons

  1. Julia H. Kim1,2,†,‡,
  2. Daniel S. Roberts1,2,†,‡,
  3. Yinghui Hu1,2,†,
  4. Garrick C. Lau1,2,†,
  5. Amy R. Brooks-Kayal3,
  6. David H. Farb2,4,
  7. Shelley J. Russek1,2

Article first published online: 28 NOV 2011

DOI: 10.1111/j.1471-4159.2011.07555.x

Issue

Journal of Neurochemistry

Journal of Neurochemistry

Volume 120, Issue 2, pages 210–219, January 2012

Additional Information

How to Cite

Kim, J. H., Roberts, D. S., Hu, Y., Lau, G. C., Brooks-Kayal, A. R., Farb, D. H. and Russek, S. J. (2012), Brain-derived neurotrophic factor uses CREB and Egr3 to regulate NMDA receptor levels in cortical neurons. Journal of Neurochemistry, 120: 210–219. doi: 10.1111/j.1471-4159.2011.07555.x

Author Information

  1. 1

    Laboratory of Translational Epilepsy, Boston University School of Medicine, Boston, Massachusetts, USA

  2. 2

    Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA

  3. 3

    Division of Neurology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, USA

  4. 4

    Laboratory of Molecular Neurobiology, Boston University School of Medicine, Boston, Massachusetts, USA

  1. †

    Program in Biomedical Neuroscience.

  2. ‡

    Shared first authorship.

*Address correspondence and reprint requests to Dr Shelley J. Russek, Division of Graduate Medical Sciences, Department of Pharmacology and Experimental Therapeutics, Laboratory of Translational Epilepsy, Boston University School of Medicine, 72 E. Concord Street, L-612, Boston, MA 02118, USA. E-mail: srussek@bu.edu

  1. †

    Program in Biomedical Neuroscience.

  2. ‡

    Shared first authorship.

Publication History

  1. Issue published online: 19 DEC 2011
  2. Article first published online: 28 NOV 2011
  3. Accepted manuscript online: 28 OCT 2011 12:37PM EST
  4. Received September 14, 2011; revised manuscript received October 20, 2011; accepted October 24, 2011.

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Keywords:

  • BDNF;
  • CREB;
  • Egr3;
  • NMDAR1;
  • ZnEgr

J. Neurochem. (2012) 120, 210–219.

Abstract

Regulation of gene expression via brain-derived neurotrophic factor (BDNF) is critical to the development of the nervous system and may well underlie cognitive performance throughout life. We now describe a mechanism by which BDNF can exert its effects on postsynaptic receptor populations that may have relevance to both the normal and diseased brain where BDNF levels either rise or fall in association with changes in excitatory neurotransmission. Increased levels of NMDA receptors (NMDARs) occur in rat cortical neurons via synthesis of new NMDA receptor 1 (NR1) subunits. The majority of synthesis is controlled by binding of cAMP response element binding protein (CREB) and early growth response factor 3 (Egr3) to the core NR1 promoter (NR1-p) region. BDNF-mediated NR1 transcription depends upon induction of the mitogen-activated protein kinase (MAPK) pathway through activation of the TrK-B receptor. Taken together with the fact that NMDAR activation stimulates BDNF synthesis, our results uncover a feed-forward gene regulatory network that may enhance excitatory neurotransmission to change neuronal behavior over time.

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