Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation
| Autor: | Michelle A. Attner, Joel M. Stein, Sara M. Cabrera, K. Matthew Lattal, Paul K. Brindle, Ted Abel, Conor B. McDonough, Joshua D. Hawk, Marcelo A. Wood, Christopher G. Vecsey, Sara A. Fabian |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Transcriptional Activation Epigenetics in learning and memory CREB Hydroxamic Acids Histone Deacetylases Article Mice Memory medicine Animals CREB-binding protein Enzyme Inhibitors Cyclic AMP Response Element-Binding Protein Histone deacetylase 5 Neuronal Plasticity biology HDAC11 Histone deacetylase 2 General Neuroscience CREB-Binding Protein Mice Mutant Strains Cell biology Histone Deacetylase Inhibitors Mice Inbred C57BL Trichostatin A Synapses biology.protein Cancer research Female Histone deacetylase medicine.drug |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(23) |
| ISSN: | 1529-2401 |
| Popis: | Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance both memory and synaptic plasticity. The current model for the action of HDAC inhibitors assumes that they alter gene expression globally and thus affect memory processes in a nonspecific manner. Here, we show that the enhancement of hippocampus-dependent memory and hippocampal synaptic plasticity by HDAC inhibitors is mediated by the transcription factor cAMP response element-binding protein (CREB) and the recruitment of the transcriptional coactivator and histone acetyltransferase CREB-binding protein (CBP) via the CREB-binding domain of CBP. Furthermore, we show that the HDAC inhibitor trichostatin A does not globally alter gene expression but instead increases the expression of specific genes during memory consolidation. Our results suggest that HDAC inhibitors enhance memory processes by the activation of key genes regulated by the CREB:CBP transcriptional complex. |
| Databáze: | OpenAIRE |
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