Neurochemical Research

, Volume 32, Issue 2, pp 363–376

Genetic Program of Neuronal Differentiation and Growth Induced by Specific Activation of NMDA Receptors

  • Cristina A. Ghiani
  • Luis Beltran-Parrazal
  • Daniel M. Sforza
  • Jemily S. Malvar
  • Akop Seksenyan
  • Ruth Cole
  • Desmond J. Smith
  • Andrew Charles
  • Pedro A. Ferchmin
  • Jean de Vellis
Original Paper


Glutamate and its receptors are expressed very early during development and may play important roles in neurogenesis, synapse formation and brain wiring. The levels of glutamate and activity of its receptors can be influenced by exogenous factors, leading to neurodevelopmental disorders. To investigate the role of NMDA receptors on gene regulation in a neuronal model, we used primary neuronal cultures developed from embryonic rat cerebri in serum-free medium. Using Affymetrix Gene Arrays, we found that genes known to be involved in neuronal plasticity were differentially expressed 24 h after a brief activation of NMDA receptors. The upregulation of these genes was accompanied by a sustained induction of CREB phosphorylation, and an increase in synaptophysin immunoreactivity. We conclude that NMDA receptor activation elicits expression of genes whose downstream products are involved in the regulation of early phases of the process leading to synaptogenesis and its consolidation, at least in part through sustained CREB phosphorylation.


N-methyl-D-Aspartate Cortical neurons DNA array Gene regulation CREB Brain development 





α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid


Brain derived neurotrophic factor


cAMP responsive element binding


CREB binding protein


Immediate early genes


Long term potentiation


Neuronal activity-regulated pentraxin


Light molecular-weight neurofilament


NGF-induced factor B


Neuron-derived orphan receptor


Phosphorylated CREB


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Cristina A. Ghiani
    • 1
  • Luis Beltran-Parrazal
    • 2
  • Daniel M. Sforza
    • 3
    • 5
  • Jemily S. Malvar
    • 1
  • Akop Seksenyan
    • 1
  • Ruth Cole
    • 1
  • Desmond J. Smith
    • 3
  • Andrew Charles
    • 2
  • Pedro A. Ferchmin
    • 4
  • Jean de Vellis
    • 1
  1. 1.Mental Retardation Research Center, Jane and Terry Semel Institute for Neuroscience and Human Behaviour, Departments of Neurobiology and Psychiatry, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  2. 2.Department of Neurology, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  3. 3.Department of Molecular and Medical Pharmacology, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  4. 4.Department of BiochemistryUniversidad Central del CaribeBayamónUSA
  5. 5.Laboratory of NeuroImaging, Department of Neurology, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA

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