Researchers identified a brain protein that could be more direct target for treating anxiety

Bridge molecule at inhibitory synapses could become a drug target for the development of new anxiolytic treatments.

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Anxiety is an important mental state and related disorders may lead to many severe sufferings. In which patients suffer from intense fears and anxiety or from sudden, inexplicable panic attacks. Whereas in extreme cases, the sufferer sometimes leaves their home and which can have many other serious impacts on their family, friend and work circles.

Recently, scientists at the Max Planck Institute for Experimental Medicine in Göttingen have discovered a synaptic protein which, when inactivated, has an anxiolytic effect in mice. This research will play an important role to study anxiety disorders.

Nearly ten percent of the total populous suffers from anxiety disorders, however, available treatment alternatives only can help a proportion of them.

Patients with anxiety disorders are commonly investigated with increased neuronal activity in the amygdala, a brain region that plays a key role in processing emotions such as anxiety or fear. Overactivation of the amygdala is found to be actively involved in causing severe anxiety.

The IgSF9b protein connects inhibitory neurons in the centromedial amygdala (left, grey area). This brain area is… [more]  © MPI f. Experimental Medicine/ Krüger-Burg
The IgSF9b protein connects inhibitory neurons in the centromedial amygdala (left, grey area). This brain area is… [more]
© MPI f. Experimental Medicine/ Krüger-Burg

Many anxiolytic medications for instance Benzodiazepines bring this overactivation to normal by strengthening the function of inhibitory synapses.

Synapses are actually connections between nerve cells in the brain, at which information is transmitted from one nerve cell to another. At inhibitory synapses, this information transmission lowers a reduction in the activity of the neighboring nerve cells.

In the amygdala, for instance, this hinders the transmission of stimuli that trigger fear and anxiety. Anxiolytic medications such as Benzodiazepines strengthen this inhibitory effect.

Unfortunately, this medication also impacts synapses in the brain those are not targeted ones. This can lead to many other side effects such as pronounced sedation and impaired concentration.

In the search for new, more specific targets for anxiolytic medications several studies take place. During such a study, healthy animals investigate an empty test chamber, rodents with a pathological anxiety phenotype split into a corner because they are afraid. Conversely, when the scientists inhibit the production of the recently discovered protein IgSF9b in these mice, they started wandering around the chamber again.

Olga Babaev from the Max Planck Institute for Experimental Medicine, said, “Blocking IgSF9b in pathologically anxious mice has an anxiolytic effect and normalizes anxiety behavior in these animals. This protein could, therefore, be a target for pharmacological approaches to treating anxiety disorders.”

Dilja Krueger-Burg, who led a study, said,  “Our research shows that protein structures at inhibitory synapses in the centromedial amygdala, and particularly the protein IgSF9b, constitute promising new targets for potential treatments. It thus provides an important contribution toward understanding the biological causes of anxiety disorders and for the development of new anxiolytic medications.”

The research was published in the journal Nature Communications.

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