liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
DNA Methylation in the Medial Prefrontal Cortex Regulates Alcohol-Induced Behavior and Plasticity
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. (Centrum för social och affektiv neurovetenskap (CSAN))
NIAAA, MD 20892 USA.
NIAAA, MD 20892 USA.
NIAAA, MD 20892 USA.
Show others and affiliations
2015 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 15, 6153-6164 p.Article in journal (Refereed) Published
Abstract [en]

Recent studies have suggested an association between alcoholism and DNA methylation, a mechanism that can mediate long-lasting changes in gene transcription. Here, we examined the contribution of DNA methylation to the long-term behavioral and molecular changes induced by a history of alcohol dependence. In search of mechanisms underlying persistent rather than acute dependence-induced neuroadaptations, we studied the role of DNA methylation regulating medial prefrontal cortex (mPFC) gene expression and alcohol-related behaviors in rats 3 weeks into abstinence following alcohol dependence. Postdependent rats showed escalated alcohol intake, which was associated with increased DNA methylation as well as decreased expression of genes encoding synaptic proteins involved in neurotransmitter release in the mPFC. Infusion of the DNA methyltransferase inhibitor RG108 prevented both escalation of alcohol consumption and dependence-induced downregulation of 4 of the 7 transcripts modified in postdependent rats. Specifically, RG108 treatment directly reversed both downregulation of synaptotagmin 2 (Syt2) gene expression and hypermethylation on CpG#5 of its first exon. Lentiviral inhibition of Syt2 expression in the mPFC increased aversion-resistant alcohol drinking, supporting a mechanistic role of Syt2 in compulsive-like behavior. Our findings identified a functional role of DNA methylation in alcohol dependence-like behavioral phenotypes and a candidate gene network that may mediate its effects. Together, these data provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcoholism.

Place, publisher, year, edition, pages
Society for Neuroscience , 2015. Vol. 35, no 15, 6153-6164 p.
Keyword [en]
alcoholism; DNA methylation; DNMT; epigenetics; neurotransmitter release; plasticity
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-118052DOI: 10.1523/JNEUROSCI.4571-14.2015ISI: 000353055600026PubMedID: 25878287OAI: oai:DiVA.org:liu-118052DiVA: diva2:812913
Available from: 2015-05-20 Created: 2015-05-20 Last updated: 2017-12-04

Open Access in DiVA

fulltext(991 kB)72 downloads
File information
File name FULLTEXT01.pdfFile size 991 kBChecksum SHA-512
91aa6f9ee4528eda7908cc59908a1b666d564f155beec540e87c4c7c957f74f30a2cdf44d90b6ec2cef814414cc90273818b802d4a1f0214d807cd5658b1353c
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Barbier, EstelleHeilig, Markus

Search in DiVA

By author/editor
Barbier, EstelleHeilig, Markus
By organisation
Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDepartment of Psychiatry
In the same journal
Journal of Neuroscience
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 72 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 180 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf