Summary: Even small amounts of alcohol can induce transcriptional and epigenomic changes in addiction-related brain regions.

Source: University of Illinois

A new rodent study shows that even small amounts of alcohol can induce epigenomic and transcriptomic changes in brain circuits critical to the development of addiction.

What’s more, researchers from the University of Illinois at Chicago who conducted the study say that the pathways involved in predisposing the brain to addiction are linked to clinical levels of depression, such as euphoria and anxiolysis, associated with higher levels of alcohol consumption. Where a person is relaxed but awake.

“This suggests that when the brain experiences alcohol’s antidepressant effects and increases mood — relaxation and excitement — it’s also being primed for alcohol use disorder,” said the study’s senior author Subhash Pandey, Joseph A. Flaherty. Professor of Psychiatry and Director of the Center for Alcohol Research in Epigenetics at the UIC College of Medicine.

Pandey said the study, for example, does not suggest that one drink leads to addiction in people, but it does offer some clues as to why some people are more vulnerable to alcohol use disorders.

“We are seeing that addictive behaviors are not always the result of long-term and high-dose experiences, but due to the rapid epigenetic changes that occur in the brain, what we show in this study can occur even at low doses,” Pandey said. who is a senior research scientist at the Jesse Brown Veterans Affairs Medical Center.

Paper published in Molecular psychiatry Pandey’s experiments studied controlled rats and alcohol exposure conditions.

In the experiments, rats were exposed to low concentrations of alcohol and their behavior was observed while exploring a maze. The researchers then analyzed the brain tissue samples collected after euthanasia by RNA sequencing and looked for gene expression patterns.

Examining the samples, the researchers found that the hypoxia inducible factor 3 alpha subunit – Hif3a, for short – was associated with changes in the brain after alcohol exposure and behavior, for example, how long mice stayed in confined spaces. (high stress) or open arms (low stress).

Alcohol increased Hif3a expression, even after low doses of exposure, and reduced anxiety. And, while many of the effects of alcohol differ between men and women, there were no differences between the two in this study.

We have seen that even small amounts of what we call “social drinking” can alter gene expression in the amygdala that regulates stress. In other words, it creates an epigenetic pathway for addiction,” Pandey said.

It shows a glass and a bottle of wine
Pandey said the study, for example, does not suggest that one drink leads to addiction in people, but it does offer some clues as to why some people are more vulnerable to alcohol use disorders. The image is in the public domain.

Pandey and his colleagues also designed additional experiments to confirm its role in relieving anxiety by blocking the gene in the amygdala of rats with or without alcohol. When Hif3a was blocked, anxiety increased in control mice, mimicking withdrawal from chronic alcohol exposure. On the other hand, this also prevents the antidepressant effects of alcohol.

And the researchers showed why. Hif3a’s chromatin – bundles of DNA and RNA – is loosely bound, meaning its genes are easily accessible for transcription.

One thing the study didn’t say, however, was what level of alcohol exposure was safe for the rats. Instead, Pandey says, it’s important to recognize that even low doses create a predisposing factor for addiction. For people, he thinks it’s easy to drink – don’t think that social drinking or even “epidemic drinking” is risk-free.

“Alcohol abuse is complex and challenging to overcome. “The information we learn from this research will help us better understand what’s going on in the brain and one day help us develop better treatments and pharmaceuticals,” Pandey said.

Co-authors of the study, titled “Unraveling epigenomic and transcriptional interactions during alcohol-induced stress,” are Harish Krishnan, Huibo Zhang, Ying Chen, John Peyton Bohnsack, Annie Shih, Handojo Kusumo, Jenny Drunevich, Chunyu Grayson, Dennis. and Mark Maienschein-Cline.

Financial support The research was supported by the National Institute on Alcohol Abuse and Alcoholism (P50AA-022538, U01AA-019971, U24AA-024605, RO1AA-010005) and the US Department of Veterans Affairs (I01BX004517, 06B0).

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This shows the closeness of planting

So neuroscience and addiction research news

Author: Jacqueline Carey
Source: University of Illinois
Contact: Jacqueline Carey – University of Illinois
Image: The image is in the public domain.

Preliminary study: Open Access.
Unraveling epigenomic and transcriptional interactions during alcohol-induced stress” by Harish Krishnan et al Molecular psychiatry


Draft

Unraveling epigenomic and transcriptional interactions during alcohol-induced stress

Positive effects of alcohol consumption, such as anxiolysis and euphoria, appear to be important factors in the initiation and maintenance of alcohol use disorder (AUD). However, the mechanisms leading from chromatin reorganization to transcriptional changes after acute ethanol exposure are unknown.

Here, we used the Assay for Transposase-Accessible Chromatin to investigate the epigenomic and transcriptional changes induced by acute ethanol sensitization using an animal model. Analysis of ATAC-seq data revealed an overall open or permissive chromatin state in the amygdala associated with pronounced changes after acute ethanol exposure.

We identified one candidate gene, Hif3a (Hypoxia-inducible factor 3, alpha subunit), which had ‘open’ chromatin regions (ATAC-seq peaks), associated with epigenetic histone acetylation signals and decreased DNA methylation at these regions.

mRNA levels Hif3a They increased with acute ethanol exposure, but decreased in the amygdala during withdrawal after chronic ethanol exposure. Knocking of Hif3a Increased ethanol intake reduced expression in the central nucleus of the amygdala Hif3a Inhibited mRNA levels and stress factors in rats.

These data indicate that chromatin accessibility and transcriptional signatures in the amygdala are under stress after ethanol exposure and may play a central role in the development of chromatin in the development of AUD.

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