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85 - Study Identifies a Signaling Molecule Involved in Resilience to Stress


Sachin Patel, M.D., Ph.D.

Vanderbilt University Medical Center

Some people are more resilient than others in the face of stress, and therefore generally at lower risk of developing mood and anxiety disorders. In a new study of mice published March 28, 2017 in Nature Communications, researchers identify a lipid signaling molecule that may play an important role in determining an individual’s degree of resilience. Lipids are fatty molecules that have many functions throughout the body.

The lipid identified by the researchers, called 2-arachidonoylglycerol (2-AG), binds to endocannabinoid receptors in brain cells, which are thought to be involved in processing anxiety, fear-associated memories and the response to stress.

In the study, the researchers divided mice into two groups based on their innate stress susceptibility, to observe anxiety-like behaviors after being subjected to stress. About a third of mice were found to be particularly susceptible, whereas the rest were classified as resilient.

Augmenting 2-AG in the brains of mice made susceptible animals more resilient to the effects of stress than they previously had been—the animals behaved less anxiously after being subjected to stress, the researchers found.

In contrast, depleting the brain of 2-AG, or blocking its receptors, resulted in previously resilient mice showing increased susceptibility to the adverse effects of stress.

Additional experiments revealed that 2-AG promotes resilience by changing communication patterns between neurons in the brain’s amygdala and ventral hippocampus, a circuit known to have an anxiety-generating function.

The findings suggest that a drug boosting 2-AG levels is a potentially useful approach for those engaged in trying to find new ways to treat stress-related psychiatric disorders, the researchers said.

The research was led Sachin Patel, M.D., Ph.D., of Vanderbilt University Medical Center, who is a 2015 Independent Investigator grantee. Collaborators on the project included Danny G. Winder, Ph.D. also of Vanderbilt University and a 2002 NARSAD Young Investigator and 2013 Distinguished Investigator grantee.

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