Depression, MicroRNA and Serotonin

The role of microRNA molecules, the small, non-coding RNA molecules which regulate various cellular activities, in the nerve cells that secrete serotonin was investigated recently by researchers at Weizmann Institute The serotonin system in the brain, when misregulated, is implicated in depression and anxiety disorders.

The team successfully identified, for the first time, the special fingerprints of a microRNA molecule that acts on the serotonin-producing nerve cells. Fusing bioinformatics methods with experiments, a connection was found between this particular microRNA, miR135, and two proteins that play a key role in serotonin production and the regulation of its activities.

Increasing MiR135 Levels

Prof. Alon Chen and PhD student Dr. Orna Issler observed that in the area of the brain containing the serotonin-producing nerve cells, miR135 levels increased when antidepressant compounds were introduced.

Mice genetically engineered to produce higher levels of the microRNA were more resistant to constant stress: They did not show any behaviors associated with chronic stress, like anxiety or depression, which would normally appear.

On the contrary, mice that had lower than average 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. They need to be low enough to enable a healthy stress response and high enough to avoid depression or anxiety disorders and to respond to serotonin-boosting antidepressants.

Bipolar Mood Disorders

When the theory 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 mood disorders.

The findings imply that miR135 might be a useful therapeutic molecule. It could be useful as both a blood test for depression and related disorders, and as a target whose levels might be raised in patient. The Weizmann Institute technology transfer department 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.

MicroRNA 135 Is Essential for Chronic Stress Resiliency, Antidepressant Efficacy, and Intact Serotonergic Activity
Issler, Orna et al.
Neuron, DOI: http://dx.doi.org/10.1016/j.neuron.2014.05.042

Image Marc Samsom, Creative Commons