Journal article
CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival
Cell death & disease, v 1(4), pp e33-e33
Apr 2010
PMID: 21364640
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repressor protein Rb, which is involved in the recruitment of chromatin modifiers (such as histone deacetylases (HDACs)) to gene promoters. In neurons, Rb controls activity-dependent genes essential to neuronal plasticity and survival, such as the
N
-methyl--aspartic acid (NMDA) receptor's subunit NR2B, the expression of which in the tetrameric ion channel largely affects calcium signaling by glutamate. In this study, we report that CXCL12 differentially modulates intracellular responses after stimulation of synaptic and extrasynaptic NMDA receptors, by a specific regulation of the NR2B gene that involves HDACs. Our results show that CXCL12 selectively inhibits NR2B expression
in vitro
and
in vivo
altering NMDA-induced calcium responses associated with neuronal death, while promoting prosurvival pathways that depend on stimulation of synaptic receptors. Along with previous studies, these findings underline the role of CXCL12/CXCR4 in the regulation of crucial components of glutamatergic transmission. These novel effects of CXCL12 may be involved in the physiological function of the chemokine in both developing and mature brains.
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Details
- Title
- CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival
- Creators
- J Nicolai - , Philadelphia, PAS Burbassi - , Philadelphia, PAJ Rubin - , St. Louis, MOO Meucci - , Philadelphia, PA
- Publication Details
- Cell death & disease, v 1(4), pp e33-e33
- Publisher
- Nature Publishing Group
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000279818300002
- Scopus ID
- 2-s2.0-79251637647
- Other Identifier
- 991014878406404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology