期刊
NEUROPHARMACOLOGY
卷 70, 期 -, 页码 168-179出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2012.12.010
关键词
Opioids; Epigenetics; ERR; MeCP2; Signal transduction; Molecular & cellular neurobiology; Neuroanatomy
资金
- Italian Telethon Foundation [GGP09196, GGP11095]
- AIRETT
- IRSF
- Progetti di Ricerca di Ateneo
- Regione Piemonte (Ricerca Sanitaria Finalizzata
- POS FESR [07/13 BANP]
- Fondazione San-Paolo
- Italian MIUR [Prin 2008KN7J7J]
Epigenetic changes such as covalent modifications of histone proteins represent complex molecular signatures that provide a cellular memory of previously experienced stimuli without irreversible changes of the genetic code. In this study we show that new gene expression induced in vivo by morphine withdrawal occurs with concomitant epigenetic modifications in brain regions critically involved in drug-dependent behaviors. We found that naloxone-precipitated withdrawal, but not chronic morphine administration, caused a strong induction of phospho-histone H3 immunoreactivity in the nucleus accumbens (NAc) shell/core and in the lateral septum (LS), a change that was accompanied by augmented H3 acetylation (lys14) in neurons of the NAc shell. Morphine withdrawal induced the phosphorylation of the epigenetic factor methyl-CpG-binding protein 2 (MeCP2) in Ser421 both in the LS and the NAc shell. These epigenetic changes were accompanied by the activation of members of the ERR pathway as well as increased expression of the immediate early genes (IEG) c-fos and activity-regulated cytoskeleton-associated protein (Arc/Arg3.1). Using a pharmacological approach, we found that H3 phosphorylation and IEG expression were partially dependent on ERK activation, while MeCP2 phosphorylation was fully ERR-independent. These findings provide new important information on the role of the ERK pathway in the regulation of epigenetic marks and gene expression that may concur to regulate in vivo the cellular changes underlying the onset of the opioid withdrawal syndrome. (C) 2013 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据