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E-GEOD-71527 - RGS9-2-controlled adaptations in the striatum determine the onset of action and eficacy of antidepressants in neuropathic pain states

Status
Released on 25 August 2015, last updated on 29 August 2015
Organism
Mus musculus
Samples (18)
Protocols (3)
Description
The striatal protein Regulator of G protein signaling-2 (RGS9-2) plays a key modulatory role in opioid, monoamine and other GPCR responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in mood reward and motivation, modulates the actions of tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc increases the efficacy of the TCA desipramine and dramatically accelerates its onset of action. By controlling the activation of effector molecules by G protein a and bg subunits, RGS9-2 affects several protein interactions, phosphoprotein levels, and the function of the epigenetic modifier histone deacetylase 5 (HDAC5), that are important for TCA responsiveness. Furthermore, information from RNA-seq analysis reveals that RGS9-2 in the NAc affects the expression of many genes known to be involved in nociception, analgesia and antidepressant drug actions. Our findings provide novel information on NAc-specific cellular mechanisms that mediate the actions of TCAs in neuropathic pain states. The RNAseq study was designed in order to reveal the impact of RGS9-2 on gene regulation in the Nucleus Accumbens under neuropathic pain and antidepressant treatment conditions. A total of 18 samples was used, coprising 6 different groups , and each group consisted of three different biological replicates.
Experiment type
RNA-seq of coding RNA 
Contacts
Vasiliki Mitsi, Venetia Zachariou
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-71527.idf.txt
Sample and data relationshipE-GEOD-71527.sdrf.txt
Additional data (1)E-GEOD-71527.additional.1.zip
Links