Study identifies molecule involved in fear extinction with potential to develop therapies for anxiety


A research team led by the University of Coimbra (UC) has identified a new mediator responsible for altering fear memories. The scientists believe that this discovery could help create new, more effective therapies for the treatment of anxiety disorders. These pathologies are marked by exaggerated or inappropriate fear and a deficit in the extinction of fear, and are one of the most prevalent health conditions worldwide, aggravated by the pandemic.
In the scientific article The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity, using a behavioral model of fear extinction, the scientists were able to identify "an increase in the activation of the TrkC protein in the amygdala - the brain region that controls the fear response - at the stage of fear extinction memory formation, which leads to an increase in synaptic plasticity [the ability of neurons to change the way they communicate with each other depending on the stimuli they receive]," explains Mónica Santos, a researcher at the UC Center for Neuroscience and Cell Biology (CNC-UC) and the Center for Innovation in Biomedicine and Biotechnology (CIBB).
Currently, one of the therapeutic options for anxiety disorders is exposure therapy, which is based on the fear extinction mechanism. However, "exposure therapies, as well as the use of drugs such as anxiolytics and antidepressants, are not 100% effective in treating these health problems and, for this reason, this research opens up new therapeutic options for this category of disorders," says Mónica Santos.
"This study validates the TrkC pathway as a potential therapeutic target for individuals with fear-related disorders, and reveals that combining exposure therapies with drugs that enhance synaptic plasticity may represent a more effective and lasting way of treating anxiety disorders," adds the research leader.
As for the next steps, the research team intends to "identify compounds that have the ability to specifically activate the TrkC molecule and thus be used as drugs allied to exposure therapy in the treatment of patients with anxiety disorders", reveals the researcher.
The research was funded by the Bial Foundation (under grant 85/18 - Role of NT3/TrkC in the regulation of fear), with the participation of other CNC-UC researchers - Gianluca Masella, Francisca Silva and Carlos B. Duarte - and researchers from the UC Faculty of Medicine, and the Department of Life Sciences. Duarte - and researchers from the UC Faculty of Medicine and the Department of Life Sciences of the UC Faculty of Science and Technology. The University of the Basque Country also participated.
The scientific article has been published in the journal Molecular Psychiatry and is available here.
Video developed by Bial about this study can be seen here.
Catarina Ribeiro, Mónica Santos e Sara Varela Amaral

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