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Credit: Academy of Finland

Researchers from Finland and the U.S. have discovered a new avenue for anti-depressant therapy, revealing new molecular information on how the brain regulates depression and anxiety.

Led by Eleanor Coffey, research director at Åbo Akademi University in Finland, the researchers found that a protein called JNK when active, represses the generation of new neurons in the hippocampus, a part of the brain that controls emotions and learning. By hindering JNK only in newly generated nerve cells in the hippocampus, the scientists were able to alleviate anxiety and depressive behavior in mice. This earlier unknown mechanism brings fresh insight on how the brain works to regulate mood and shows that inhibitors of JNK can provide a new path for anti-depressant and anxiolytic drug development.

“In a variety of tests for anxiety, and later in tests for depressive-like behavior, there was a substantial amelioration in knockout mice,” Coffey told DDD in an exclusive interview. "We validated these initial findings using a variety of methods to inhibit JNK. It then became very clear the JNK played a dominant role in controlling this behavior and we continued working to understand the mechanism."

Eleanor Coffey
Research Director, Åbo Akademi University, Finland

Both anxiety and depression are highly widespread disorders and account for one of the largest causes of disability worldwide. These results are crucial since many patients don’t respond to current treatments and it’s been long known that new mechanistic understanding of these disorders would be needed to identify drugs for treatment-resistant depression.

The researchers used virus tools to seek where in the brain the JNK inhibitor acted to improve mood. They discovered the molecule acts to alleviate anxiety and depression by controlling newly born nerve cells in the hippocampus.

The group's expertise is in preclinical research. The researchers are continuing to assess the feasibility of inhibiting this target for treatment of anxiety and depression in animal models.

"This discovery opens up a rationale for developing new drugs for anxiety and depression," Coffey added. "Indeed many JNK inhibitors have been developed already. Some are undergoing clinical testing for various indications."

"At the very least, anxiety and depression should be scored in individuals undergoing trials with JNK inhibitors to see if there is a benefit. Developing drugs for brain disorders is however fraught with challenges, but we must try," she concluded.

This research was funded by the EU-funded Marie Curie Initial Training Network r’BIRTH, by the Academy of Finland, Turku Network in Molecular Biosciences and the national Institute of Aging (U.S.). This study was published in the Nature Publishing Group journal Molecular Psychiatry.

 

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