PMID- 29155278
OWN - NLM
STAT- MEDLINE
DCOM- 20190218
LR  - 20210109
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 369
DP  - 2018 Jan 15
TI  - MeCP2 Expression in a Rat Model of Risky Decision Making.
PG  - 212-221
LID - S0306-4522(17)30810-2 [pii]
LID - 10.1016/j.neuroscience.2017.11.016 [doi]
AB  - Many neuropsychiatric disorders are associated with abnormal decision making 
      involving risk of punishment, but the underlying molecular basis remains poorly 
      understood. Methyl CpG-binding protein 2 (MeCP2) is an epigenetic factor that 
      regulates transcription by directly binding to methylated DNA. Here, we evaluated 
      MeCP2 expression in the context of risk-taking behaviors using the Risky 
      Decision-making Task (RDT), in which rats make discrete choices between a small 
      "safe" food reward and a large "risky" food reward accompanied by varying 
      probabilities of punishment. In Experiment 1, expression of MeCP2 as assessed by 
      immunoblotting in the medial prefrontal cortex (mPFC), but not the striatum, was 
      inversely correlated with the degree of preference for the large, risky reward 
      (risk taking) seven days after the last RDT test. In Experiment 2, MeCP2 
      expression 90 min after RDT testing, assessed using immunohistochemistry, was 
      suppressed in both the dorsal mPFC (dmPFC) and nucleus accumbens compared to home 
      cage controls, indicating that MeCP2 expression is modulated by RDT performance. 
      Additional experiments revealed that RDT performance increased expression of 
      MeCP2 phosphorylated at Ser421 (associated with neuronal activity and activation 
      of gene expression) in dmPFC principal neurons. Finally, as in Experiment 1, 
      lower expression of MeCP2 in the ventral mPFC was associated with greater risk 
      taking under baseline conditions. Together, these findings indicate a complex 
      regulatory role of MeCP2 in risky decision making, and suggest that epigenetic 
      factors may be an important component of the molecular mechanisms underlying such 
      decision-making processes.
CI  - Copyright (c) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Deng, Jay V
AU  - Deng JV
AD  - Department of Psychiatry, University of Florida College of Medicine, United 
      States; Center for Addiction Research and Education, University of Florida, 
      United States. Electronic address: jaydeng@ufl.edu.
FAU - Orsini, Caitlin A
AU  - Orsini CA
AD  - Department of Psychiatry, University of Florida College of Medicine, United 
      States.
FAU - Shimp, Kristy G
AU  - Shimp KG
AD  - Department of Neuroscience, University of Florida College of Medicine, United 
      States.
FAU - Setlow, Barry
AU  - Setlow B
AD  - Department of Psychiatry, University of Florida College of Medicine, United 
      States; Department of Neuroscience, University of Florida College of Medicine, 
      United States; Department of Psychology, University of Florida, United States; 
      Center for Addiction Research and Education, University of Florida, United 
      States. Electronic address: setlow@ufl.edu.
LA  - eng
GR  - K99 DA041493/DA/NIDA NIH HHS/United States
GR  - R01 DA036534/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171116
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Methyl-CpG-Binding Protein 2)
SB  - IM
MH  - Animals
MH  - Corpus Striatum/metabolism
MH  - Decision Making/*physiology
MH  - Male
MH  - Methyl-CpG-Binding Protein 2/biosynthesis/metabolism/*physiology
MH  - Nucleus Accumbens/metabolism
MH  - Phosphorylation
MH  - Prefrontal Cortex/metabolism
MH  - Punishment
MH  - Rats
MH  - Reward
MH  - *Risk-Taking
MH  - Time Factors
PMC - PMC5766376
MID - NIHMS925569
OTO - NOTNLM
OT  - DNA methylation
OT  - MeCP2
OT  - decision making
OT  - epigenetics
OT  - medial prefrontal cortex
OT  - risk taking
EDAT- 2017/11/21 06:00
MHDA- 2019/02/20 06:00
PMCR- 2019/01/15
CRDT- 2017/11/21 06:00
PHST- 2017/05/19 00:00 [received]
PHST- 2017/10/23 00:00 [revised]
PHST- 2017/11/10 00:00 [accepted]
PHST- 2017/11/21 06:00 [pubmed]
PHST- 2019/02/20 06:00 [medline]
PHST- 2017/11/21 06:00 [entrez]
PHST- 2019/01/15 00:00 [pmc-release]
AID - S0306-4522(17)30810-2 [pii]
AID - 10.1016/j.neuroscience.2017.11.016 [doi]
PST - ppublish
SO  - Neuroscience. 2018 Jan 15;369:212-221. doi: 10.1016/j.neuroscience.2017.11.016. 
      Epub 2017 Nov 16.