Aging-related protein may play role in depression

SIRT1 study in mice suggests possible new treatment target

A busy protein known for its role in aging may also have a hand in depression, a study on mice hints. Under certain circumstances, the aging-related SIRT1 protein seems to make mice despondent, scientists report August 10 in the Journal of Neuroscience. The results are preliminary, but they might ultimately help find new depression treatments.

Today’s treatments aren’t always effective, and new approaches are sorely needed. “This is one potential new avenue,” says study coauthor Deveroux Ferguson of the University of Arizona College of Medicine in Phoenix.

Ferguson and colleagues subjected mice to 10 days of stressful encounters with other mice. After their demoralizing ordeal, the mice showed signs of depression, such as eschewing sugar water and giving up attempts to swim. Along with these signs of rodent despair, the mice had more SIRT1 gene activity in the nucleus accumbens, a brain area that has been linked to motivation and depression.

Resveratrol, a compound found in red grapes, supercharges the SIRT1 protein, making it more efficient at its job. When Ferguson and colleagues delivered resveratrol directly to the nucleus accumbens, mice displayed more signs of depression and anxiety. When the researchers used a different compound to hinder SIRT1 activity, the mice showed the opposite effect, appearing bolder in some tests than mice that didn’t receive the compound.

SIRT1 is a type of protein known as a histone deacetylase, which can change the way some genes behave. In that way, SIRT1 can influence many cellular processes such as metabolism, development and even cancer — a wide-ranging job description that may confound attempts to interfere with it to treat depression.

A study published last year in Nature described a genetic signature near the SIRT1 gene that was more common in over 5,000 Chinese women with depression than in those without the disorder. With that in mind, the new work is “clearly important and interesting, and there is a possibility that it might lead somewhere,” says psychiatrist Jonathan Flint of UCLA, who coauthored the study in Nature.

He cautions that his study turned up a proximity — not a definite match. More work is needed to show that the SIRT1 gene is actually involved in depression. 

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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