Thursday , December 9 2021

Researchers are identifying anti-inflammatory mechanisms that promote alcohol dependence



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Inside the brain, a small almond-shaped region called the amygdala plays a vital role in showing emotion, behavior, and motivation. It is understandable that he is also heavily involved in alcohol abuse, and Marisa Roberto, Ph.D., is a professor in the Department of Molecular Medicine at Scripps Research.

Now, for the first time, Roberto and his team have identified significant changes in anti-inflammatory mechanisms and cellular activity that promote alcohol dependence. By counteracting this process in mice, they managed to stop the excessive consumption of alcohol – revealing a possible way of treating the disorder of alcohol consumption. The research was published in Advances in neurobiology.

We found that chronic exposure to alcohol endangers immune cells in the brain, which are important for maintaining healthy neurons. The damage caused by this can lead to anxiety and drinking alcohol that can lead to a disorder of alcohol consumption. “

Reesha Patel, PhD, first author of the research and postdoctoral fellow, Robert’s Laboratory

Robert’s research looked at an immune protein called Interleukin 10 or IL-10 that dominates the brain. IL-10 is known to have strong anti-inflammatory properties, which ensures that the immune system does not respond too strongly to disease threats. In the brain, IL-10 helps limit inflammation caused by injury or disease, such as stroke or Alzheimer’s. It also seems to have an impact on key behaviors associated with chronic alcohol consumption.

In mice with chronic alcohol use, IL-10 significantly reduced amygdala and did not properly target neurons, increasing alcohol consumption. However, by encouraging IL-10 signaling in the brain, scientists can reverse the rich effects. It is noteworthy that anxiety-like behaviors and motivation to drink alcohol are significantly reduced.

“We have shown that inflammatory responses in the brain are highly at stake in the development and maintenance of alcohol use disorders,” says Roberto. “But, more importantly, we offered a new framework for therapeutic intervention, pointing to anti-inflammatory mechanisms.”

Alcohol consumption disorder is widespread, affecting about 15 million people in the United States, and there are few effective treatments. By studying how brain cells change with prolonged exposure to alcohol, Robert’s lab has discovered a number of new therapeutic approaches for those with alcohol addiction.

In the latest research, Robert’s lab collaborated with Dr. Silke Paust, an associate professor in the Department of Immunology and Microbiology. Paust and his team have determined whole-brain immune cells caused by chronic alcohol consumption.

The findings showed a major change in the immune landscape of the brain, increasing the level of immune cells known as microglia and T-regulatory cells, which produce IL-10.

Despite a higher number of cells producing IL-10 throughout the brain of mice with long alcohol use, the amygdala told a different story. In that region, the level of IL-10 was lower and their signaling function was compromised. The immune system in the amygdala suggests that it responds in a unique way to chronic alcohol use.

This research completes the latest findings from Roberto’s lab, demonstrating the role that micrology plays in the development of alcohol dependence.

Future research will build on these findings to determine how and when IL-10 signals to alter tonsil neurons and other brain circuits associated with additions.

Source:

Scripps Research Institute

Journal reference:

Patel, RR, et al. (2020) IL-10 normalizes amygdala-rich GABA transmission and reverses the escalation caused by anxiety-like behavior and alcohol dependence. Advances in neurobiology. doi.org/10.1016/j.pneurobio.2020.101952.

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