Genetic program of neuronal differentiation and growth induced by specific activation of NMDA receptors.
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.
Ghiani
Cristina A
CA
Mental Retardation Research Center, Jane and Terry Semel Institute for Neuroscience and Human Behaviour, Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Beltran-Parrazal
Luis
L
Sforza
Daniel M
DM
Malvar
Jemily S
JS
Seksenyan
Akop
A
Cole
Ruth
R
Smith
Desmond J
DJ
Charles
Andrew
A
Ferchmin
Pedro A
PA
de Vellis
Jean
J
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000096:biosynthesis
D017362:Cyclic AMP Response Element-Binding Protein; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D016202:N-Methylaspartate