The expression of spinal methyl-CpG-binding protein 2, DNA methyltransferases and histone deacetylases is modulated in persistent pain statesReport as inadecuate




The expression of spinal methyl-CpG-binding protein 2, DNA methyltransferases and histone deacetylases is modulated in persistent pain states - Download this document for free, or read online. Document in PDF available to download.

Molecular Pain

, 8:14

First Online: 27 February 2012Received: 06 October 2011Accepted: 27 February 2012

Abstract

BackgroundDNA CpG methylation is carried out by DNA methyltransferases and induces chromatin remodeling and gene silencing through a transcription repressor complex comprising the methyl-CpG-binding protein 2 MeCP2 and a subset of histone deacetylases. Recently, we have found that MeCP2 activity had a crucial role in the pattern of gene expression seen in the superficial dorsal horn rapidly after injection of Complete Freund-s Adjuvant CFA in the rat ankle joint. The aim of the present study was to analyse the changes in expression of MeCP2, DNA methyltransferases and a subset of histone deacetylases in the superficial dorsal horn during the maintenance phase of persistent pain states. In this process, the cell specific expression of MeCP2 was also investigated.

ResultsUsing immunohistochemistry, we found that neurones, oligodendrocytes and astrocytes expressed MeCP2. Microglia, oligodendrocyte precursor cells and Schwann cells never showed any positive stain for MeCP2. Quantitative analyses showed that MeCP2 expression was increased in the superficial dorsal horn 7 days following CFA injection in the ankle joint but decreased 7 days following spared nerve injury. Overall, the expression of DNA methyltransferases and a subset of histone deacetylases followed the same pattern of expression. However, there were no significant changes in the expression of the MeCP2 targets that we had previously shown are regulated in the early time points following CFA injection in the ankle joint. Finally, the expression of MeCP2 was also down regulated in damaged dorsal root ganglion neurones following spared nerve injury.

ConclusionOur results strongly suggest that changes in chromatin compaction, regulated by the binding of MeCP2 complexes to methylated DNA, are involved in the modulation of gene expression in the superficial dorsal horn and dorsal root ganglia during the maintenance of persistent pain states.

KeywordsMeCP2 Astrocyte Microglia Spinal nerve injury Inflammation Chronic pain DNA methyltransferase Histone deacetylase AbbreviationsAPCAdenomatosis Polyposis Coli

ATF3anti-Activating Transcription Factor 3

CFAComplete Freund-s Adjuvant

DNMTDNA methyl transferase

DRGdorsal root ganglion

FKBP5FK 506 binding protein 5: GFAP: Glial Fibrillary Acidic Protein

HDACHistone deacetylase

IBa1anti-Ionized calcium-binding adaptor molecule 1

KOknock-out

MeCP2Methyl-CpG-binding protein 2

OPColigodendrocyte precursor cells

SGK1serum- and glucocorticoid- regulated kinase

SNIspared nerve injury

SULT1A1sulfotransferase family 1A: phenol-preferring: member 1.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-14 contains supplementary material, which is available to authorized users.

Keri K Tochiki, Joel Cunningham contributed equally to this work.

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Author: Keri K Tochiki - Joel Cunningham - Stephen P Hunt - Sandrine M Géranton

Source: https://link.springer.com/







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