UIC discovery could lead to new treatments for alcohol use disorders and depression

A discovery by researchers at the University of Illinois at Chicago could lead to new treatments for people with alcohol use disorders and depression.

The study, “Transcriptomics identifies STAT3 as a key regulator of hippocampal and anhedonia gene expression during withdrawal from chronic alcohol exposure,” is published in the journal Translational Psychiatry by researchers at the UIC Center for Research on Alcohol in Epigenetics.

During long-term alcohol withdrawal, people often experience depression, which can cause them to start drinking again as a way to heal themselves. If we can deal with this aspect, we hope we can prevent people from relapsing. “

Amy Lasek, UIC Associate Professor of Psychiatry, Anatomy and Cell Biology, Faculty of Medicine and Study Author

Withdrawing from chronic alcohol use can often lead to depression. For this study, the researchers took post-mortem hippocampal samples from alcohol-withdrawn rats. The hippocampus is a region of the brain that plays a role in depression and cognitive function. The researchers performed RNA sequencing of all RNA transcripts in the hippocampus and looked for those that had been altered during alcohol withdrawal.

One of the RNA transcripts that has been altered produces a protein called STAT3. STAT3 is a transcription factor that controls the expression of many different genes, including immune response genes. Notably, several known genes regulated by STAT3 were also increased in the hippocampus during alcohol withdrawal, indicating that STAT3 could be a “major regulator” of several genes in the hippocampus during withdrawal.

The rats were treated during weaning with a compound which blocks the activity of STAT3. The anhedonia induced by weaning rats, or the inability to experience pleasure, was alleviated.

In addition, the researchers examined the same genes in human postmortem hippocampus samples from individuals with a medical diagnosis of alcohol use disorder, alcoholism. They found that STAT3 and its target genes were elevated in the postmortem hippocampus of deceased human subjects without alcohol in their system – either withdrawing or abstaining from alcohol – compared to samples from control subjects who did not have the disorder. of alcohol consumption. These results were surprisingly similar to the results found in the rat study.

“The studies in humans and rats are similar, which could mean that our results in rats can potentially be applied to humans. We have not done any treatment for people with alcohol use disorders, but we can see from the rat data that if we block it during weaning we can relieve depression, ”Lasek said.

Certain genes regulated by STAT3 are involved in the innate immune response in the brain. There is a known link between the overactive immune response and major depressive disorder, Lasek said.

“We know that chronic alcohol consumption can induce an immune response in the brain. By inhibiting STAT3, we believe that we dampen this overactive immune response by blocking the ability of STAT3 to increase the expression of these immune response genes during weaning, Lasek mentioned.

Lasek said inflammation in the brain is currently a hot topic of research and that further research could determine whether dampening the brain’s inflammatory response could treat psychiatric disorders.

Currently available antidepressants are not effective in reducing alcohol consumption. And other drugs available to treat alcohol use disorders are not universally effective. Further study for a better understanding of how STAT3 works could hopefully lead to more effective interventions for alcohol use disorders and associated depression, Lasek said.

Source:

Journal reference:

Chen, WY., et al. (2021) Transcriptomics identifies STAT3 as a key regulator of hippocampal and anhedonia gene expression during withdrawal from chronic alcohol exposure. Translational Psychiatry. doi.org/10.1038/s41398-021-01421-8.


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