Tiny molecule could help diagnose and treat mental disorders

June 19, 2014

According the World Health Organization, such mood disorders as depression affect some 10% of the world's population and are associated with a heavy burden of disease. That is why numerous scientists around the world have invested a great deal of effort in understanding these diseases. Yet the molecular and cellular mechanisms that underlie these problems are still only partly understood.

The existing anti-depressants are not good enough: Some 60-70% of patients get no relief from them. For the other 30-40%, that relief is often incomplete, and they must take the drugs for a long period before feeling any effects. In addition, there are many side effects associated with the drugs. New and better drugs are clearly needed, an undertaking that requires, first and foremost, a better understanding of the processes and causes underlying the disorders.

The Weizmann Institute's Prof. Alon Chen, together with his then PhD student Dr. Orna Issler, investigated the molecular mechanisms of the brain's serotonin system, which, when misregulated, is involved in depression and anxiety disorders. Chen and his colleagues researched the role of microRNA molecules (small, non-coding RNA molecules that regulate various cellular activities) in the that produce serotonin. They succeeded in identifying, for the first time, the unique "fingerprints" of a microRNA molecule that acts on the serotonin-producing nerve cells. Combining bioinformatics methods with experiments, the researchers found a connection between this particular microRNA, (miR135), and two proteins that play a key role in serotonin production and the regulation of its activities. The findings appeared today in Neuron.

The scientists noted that in the area of the brain containing the serotonin-producing nerve cells, miR135 levels increased when antidepressant compounds were introduced. Mice that were genetically engineered to produce higher-than-average amounts of the microRNA were more resistant to constant stress: They did not develop any of the behaviors associated with chronic stress, such as anxiety or depression, which would normally appear. In contrast, mice that expressed low levels of miR135 exhibited more of these behaviors; in addition, their response to antidepressants was weaker. In other words, the brain needs the proper miR135 levels – low enough to enable a healthy stress response and high enough to avoid depression or anxiety disorders and to respond to serotonin-boosting antidepressants. When this idea was tested on human blood samples, the researchers found that subjects who suffered from depression had unusually low miR135 levels in their blood. On closer inspection, the scientists discovered that the three genes involved in producing miR135 are located in areas of the genome that are known to be associated with risk factors for bipolar .

These findings suggest that miR135 could be a useful therapeutic molecule – both as a blood test for and related disorders, and as a target whose levels might be raised in patients. Yeda Research and Development Co. Ltd., the technology transfer arm of the Weizmann Institute, has applied for a patent connected to these findings and recently licensed the rights to miCure Therapeutics to develop a drug and diagnostic method. After completing preclinical trials, the company hopes to begin clinical trials in humans.

Prof. Alon Chen is the Head of the Max Planck Society - Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics.

Prof. Alon Chen's research is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Perlman Family Foundation, Founded by Louis L. and Anita M. Perlman; the Adelis Foundation; the Irving I Moskowitz Foundation; the European Research Council; and the Ruhman Family Laboratory for Research in the Neurobiology of Stress.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

Explore further: A tiny molecule may help battle depression

Related Stories

A tiny molecule may help battle depression

June 8, 2014
Levels of a small molecule found only in humans and in other primates are lower in the brains of depressed individuals, according to researchers at McGill University and the Douglas Institute. This discovery may hold a key ...

Switching off anxiety with light

April 7, 2014
Receptors for the messenger molecule serotonin can be modified in such a way that they can be activated by light. Together with colleagues, neuroscientists from the Ruhr-Universität Bochum (RUB) report on this finding in ...

The secret life of serotonin

June 10, 2014
As a graduate student, Chris Skipwith studied cardiovascular disease and was particularly interested in the biophysics of the proteins involved in blood clotting. "We were very interested in how clotting is related to the ...

Psilocybin inhibits the processing of negative emotions in the brain

May 7, 2014
Emotions like fear, anger, sadness, and joy enable people to adjust to their environment and react flexibly to stress and strain and are vital for cognitive processes, physiological reactions, and social behaviour. The processing ...

Depression is detectable in the blood

April 30, 2014
Researchers at the MedUni Vienna have demonstrated the possibility of using a blood test to detect depression. While blood tests for mental illnesses have until recently been regarded as impossible, a recent study clearly ...

Recommended for you

Laser used to reawaken lost memories in mice with Alzheimer's disease

July 26, 2017
(Medical Xpress)—A team of researchers at Columbia University has found that applying a laser to the part of a mouse brain used for memory storage caused the mice to recall memories lost due to a mouse version of Alzheimer's ...

Cellular roots of anxiety identified

July 26, 2017
From students stressing over exams to workers facing possible layoffs, worrying about the future is a normal and universal experience. But when people's anticipation of bad things to come starts interfering with daily life, ...

Cognitive cross-training enhances learning, study finds

July 25, 2017
Just as athletes cross-train to improve physical skills, those wanting to enhance cognitive skills can benefit from multiple ways of exercising the brain, according to a comprehensive new study from University of Illinois ...

Brain disease seen in most football players in large report

July 25, 2017
Research on 202 former football players found evidence of a brain disease linked to repeated head blows in nearly all of them, from athletes in the National Football League, college and even high school.

Lutein may counter cognitive aging, study finds

July 25, 2017
Spinach and kale are favorites of those looking to stay physically fit, but they also could keep consumers cognitively fit, according to a new study from University of Illinois researchers.

Zebrafish study reveals clues to healing spinal cord injuries

July 25, 2017
Fresh insights into how zebrafish repair their nerve connections could hold clues to new therapies for people with spinal cord injuries.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.