We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Inhibition of cAMP response element-binding protein reduces neuronal excitability and plasticity, and triggers neurodegeneration.
- Authors
Jancic, Dragana; Lopez de Armentia, Mikel; Valor, Luis M; Olivares, Roman; Barco, Angel
- Abstract
The cAMP-responsive element-binding protein (CREB) pathway has been involved in 2 major cascades of gene expression regulating neuronal function. The first one presents CREB as a critical component of the molecular switch that controls long-lasting forms of neuronal plasticity and learning. The second one relates CREB to neuronal survival and protection. To investigate the role of CREB-dependent gene expression in neuronal plasticity and survival in vivo, we generated bitransgenic mice expressing A-CREB, an artificial peptide with strong and broad inhibitory effect on the CREB family, in forebrain neurons in a regulatable manner. The expression of A-CREB in hippocampal neurons impaired L-LTP, reduced intrinsic excitability and the susceptibility to induced seizures, and altered both basal and activity-driven gene expression. In the long-term, the chronic inhibition of CREB function caused severe loss of neurons in the CA1 subfield as well as in other brain regions. Our experiments confirmed previous findings in CREB-deficient mutants and revealed new aspects of CREB-dependent gene expression in the hippocampus supporting a dual role for CREB-dependent gene expression regulating intrinsic and synaptic plasticity and promoting neuronal survival.
- Publication
Cerebral cortex (New York, N.Y. : 1991), 2009, Vol 19, Issue 11, p2535
- ISSN
1460-2199
- Publication type
Journal Article
- DOI
10.1093/cercor/bhp004