PMID- 24990928
OWN - NLM
STAT- MEDLINE
DCOM- 20140829
LR  - 20220310
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 34
IP  - 27
DP  - 2014 Jul 2
TI  - MeCP2 repression of G9a in regulation of pain and morphine reward.
PG  - 9076-87
LID - 10.1523/JNEUROSCI.4194-13.2014 [doi]
AB  - Opioids are commonly used for pain relief, but their strong rewarding effects 
      drive opioid misuse and abuse. How pain affects the liability of opioid abuse is 
      unknown at present. In this study, we identified an epigenetic regulating cascade 
      activated by both pain and the opioid morphine. Both persistent pain and repeated 
      morphine upregulated the transcriptional regulator MeCP2 in mouse central nucleus 
      of the amygdala (CeA). Chromatin immunoprecipitation analysis revealed that MeCP2 
      bound to and repressed the transcriptional repressor histone dimethyltransferase 
      G9a, reducing G9a-catalyzed repressive mark H3K9me2 in CeA. Repression of G9a 
      activity increased expression of brain-derived neurotrophic factor (BDNF). 
      Behaviorally, persistent inflammatory pain increased the sensitivity to acquiring 
      morphine-induced, reward-related behavior of conditioned place preference in 
      mice. Local viral vector-mediated MeCP2 overexpression, Cre-induced G9a 
      knockdown, and CeA application of BDNF mimicked, whereas MeCP2 knockdown 
      inhibited, the pain effect. These results suggest that MeCP2 directly represses 
      G9a as a shared mechanism in central amygdala for regulation of emotional 
      responses to pain and opioid reward, and for their behavioral interaction.
CI  - Copyright (c) 2014 the authors 0270-6474/14/349076-12$15.00/0.
FAU - Zhang, Zhi
AU  - Zhang Z
AUID- ORCID: 0000-0002-4205-3181
AD  - Department of Anesthesiology and Pain Medicine, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas 77030, Key Laboratory of Brain Functions 
      and Diseases, School of Life Science, University of Science and Technology of 
      China, Hefei, Anhui 230027, China, and.
FAU - Tao, Wenjuan
AU  - Tao W
AD  - Key Laboratory of Brain Functions and Diseases, School of Life Science, 
      University of Science and Technology of China, Hefei, Anhui 230027, China, and.
FAU - Hou, Yuan-Yuan
AU  - Hou YY
AD  - Department of Anesthesiology and Pain Medicine, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas 77030.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Anesthesiology and Pain Medicine, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas 77030.
FAU - Kenny, Paul J
AU  - Kenny PJ
AD  - Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at 
      Mount Sinai, New York, New York 10029.
FAU - Pan, Zhizhong Z
AU  - Pan ZZ
AD  - Department of Anesthesiology and Pain Medicine, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas 77030, zzpan@mdanderson.org.
LA  - eng
GR  - DA025983/DA/NIDA NIH HHS/United States
GR  - DA027541/DA/NIDA NIH HHS/United States
GR  - DA023069/DA/NIDA NIH HHS/United States
GR  - R01 DA027541/DA/NIDA NIH HHS/United States
GR  - R01 DA023069/DA/NIDA NIH HHS/United States
GR  - R01 DA025983/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Mecp2 protein, mouse)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Narcotics)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 76I7G6D29C (Morphine)
RN  - EC 2.1.1.43 (G9a protein, mouse)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
SB  - IM
MH  - Amygdala/*physiopathology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/genetics/pharmacology
MH  - Chronic Pain/drug therapy/etiology/*physiopathology
MH  - Conditioning, Classical/physiology
MH  - Crosses, Genetic
MH  - Disease Susceptibility
MH  - Down-Regulation
MH  - Emotions/physiology
MH  - Epigenesis, Genetic
MH  - Exploratory Behavior/drug effects
MH  - Female
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Genetic Vectors
MH  - Histone-Lysine N-Methyltransferase/*physiology
MH  - Male
MH  - Methyl-CpG-Binding Protein 2/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Morphine/*pharmacology/therapeutic use/toxicity
MH  - Morphine Dependence/etiology/psychology
MH  - Narcotics/*pharmacology/therapeutic use/toxicity
MH  - Nerve Tissue Proteins/genetics/physiology
MH  - Recombinant Fusion Proteins/metabolism
MH  - Reinforcement, Psychology
MH  - *Reward
MH  - Transgenes
PMC - PMC4078085
OTO - NOTNLM
OT  - G9a
OT  - MeCP2
OT  - opioid
OT  - pain
OT  - reward
COIS- The authors declare no financial conflict of interest.
EDAT- 2014/07/06 06:00
MHDA- 2014/08/30 06:00
PMCR- 2015/01/02
CRDT- 2014/07/04 06:00
PHST- 2014/07/04 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2014/08/30 06:00 [medline]
PHST- 2015/01/02 00:00 [pmc-release]
AID - 34/27/9076 [pii]
AID - 4194-13 [pii]
AID - 10.1523/JNEUROSCI.4194-13.2014 [doi]
PST - ppublish
SO  - J Neurosci. 2014 Jul 2;34(27):9076-87. doi: 10.1523/JNEUROSCI.4194-13.2014.