Alcoholism is a multifaceted disorder caused by both genetic and environmental influences and epigenetic modifications, including histone acetylation and DNA methylation, have been shown to control alcohol-related behaviors. In a recent study, Estelle Barbier, from Linköping University in Sweden, collaborated with scientists at NIH to begin to understand how DNA methylation contributes to the lasting neuroadaptive changes brought on from a history of alcohol dependence.
The team first investigated global DNA methylation patterns in different regions of the brain associated with addiction and found increased methylation in the medial prefrontal cortex of alcohol-dependent rats. DNA methyltransferase 1 (DNMT1) protein, one of three DNMT isoforms, was overexpressed in the mPFC and specifically in neurons.
These findings aligned with previous studies that showed neurons are epigenetically more sensitive to environmental circumstances. Pharmacological inhibition of DNA methylation prevented escalated intake by post-dependent rats, but had no effect on control animals; DNA methylation levels in the mPFC were altered in accordance with the behavioral results. Inhibition of DNMT also decreased the level of alcohol intake in dependent rats when it was administered following three weeks of abstinence, indicating that is causally involved in the longer term neuroadaptive changes that modulate alcohol-related behaviors. Lastly, the investigators showed that chronic intermittent alcohol exposure altered the expression of many genes and that DNMT inhibition prevented alcolhol-dependent down-regulation of several neurotransmitter genes in the mPFC.
It is common for people with an addiction to alcohol to relapse during prolonged periods of sobriety. The work by Barbier, et al suggests that pharmacological modulation of DNA methylation may aid people in achieving and maintaining sobriety.
Learn more about the Transcreener® EPIGEN Methylatransferase Assay, which provides universal methyltransferase detection using any substrate.