Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice

Baker-Andresen, Danay, Zhao, Qiongyi, Li, Xiang, Jupp, Bianca, Chesworth, Rose, Lawrence, Andrew J. and Bredy, Timothy (2015) Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice. Neuroepigenetics, 4 1-11. doi:10.1016/j.nepig.2015.10.001


Author Baker-Andresen, Danay
Zhao, Qiongyi
Li, Xiang
Jupp, Bianca
Chesworth, Rose
Lawrence, Andrew J.
Bredy, Timothy
Title Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice
Journal name Neuroepigenetics   Check publisher's open access policy
ISSN 2214-7845
Publication date 2015-10-01
Sub-type Article (original research)
DOI 10.1016/j.nepig.2015.10.001
Open Access Status DOI
Volume 4
Start page 1
End page 11
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Abstract Continued vulnerability to relapse during abstinence is a characteristic of cocaine addiction and suggests that drug-induced neuroadaptations persist during abstinence. However, the precise cellular and molecular attributes of these adaptations remain equivocal. One possibility is that cocaine self-administration leads to enduring changes in DNA methylation. To address this possibility, we isolated neurons from medial prefrontal cortex and performed high throughput DNA sequencing to examine changes in DNA methylation following cocaine self-administration. Twenty-nine genomic regions became persistently differentially methylated during cocaine self-administration, and an additional 28 regions became selectively differentially methylated during abstinence. Altered DNA methylation was associated with isoform-specific changes in the expression of co-localizing genes. These results provide the first neuron-specific, genome-wide profile of changes in DNA methylation induced by cocaine self-administration and protracted abstinence. Moreover, our findings suggest that altered DNA methylation facilitates long-term behavioral adaptation in a manner that extends beyond the perpetuation of altered transcriptional states.
Keyword Cocaine self-administration
DNA methylation
Genome-wide
MBD
Neuron
Next-generation sequencing
Relapse
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
 
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