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.

Scientists believe this discovery could help create new, more effective therapies for treating anxiety disorders. These pathologies are marked by exaggerated or inappropriate fear and a deficit in extinguishing fear, being one of the most prevalent health conditions worldwide, worsened 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 behavioural model of fear extinction, scientists were able to identify “an increase in the activation of the TrkC protein in the amygdala – the region brain that controls the fear response – in the phase of fear extinction memory formation, which leads to an increase in synaptic plasticity [capacity of neurons to change the way they communicate with each other depending on the stimuli they receive]”, explains the researcher at the UC Center for Neuroscience and Cell Biology (CNC-UC) and the Center for Innovation in Biomedicine and Biotechnology (CIBB), Mónica Santos.

Currently, one of the therapeutic options for anxiety disorders is exposure therapies, which are 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, therefore, this research opens up new therapeutic options for this category of disorders”, advances Mónica Santos.

This study validates the TrkC pathway as a potential therapeutic target for individuals with fear-related illnesses, and reveals that combining exposure therapies with drugs that enhance synaptic plasticity may represent a more effective and long-lasting way to treat disorders of anxiety”, adds the also leader of the investigation.

As for the next steps, the research team intends to “identify compounds that can specifically activate the TrkC molecule and, thus, be used as drugs combined with exposure therapy in the treatment of patients with anxiety disorders”, reveals the investigator.

The research was financed by the Bial Foundation (within the scope of the 85/18 funding grant – Role of NT3/TrkC in the regulation of fear), with the participation of other researchers from CNC-UC – Gianluca Masella, Francisca Silva and Carlos B. 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 is published in the journal Molecular Psychiatry and is available at the link.

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