An international team of scientists has discovered a gene in the brain that drives anxiety symptoms.
The discovery offers a promising new drug target for anxiety disorders.
Researchers from the Universities of Bristol and Exeter led the study, which was published in Nature Communications.
Anxiety disorders are common, with one in four people being diagnosed with a disorder at least once in their lifetime.
However, currently, available anti-anxiety drugs have limited efficacy. More than half of the patients do not achieve remission following treatment.
The poor understanding of the neural circuits underlying anxiety and molecular events resulting in stress-related neuropsychiatric states is responsible for the limited success of developing potent anti-anxiety drugs.
Identifying the Molecular Events in the Brain that Underpin Anxiety
The researchers focused on a group of molecules called miRNAs in animal models.
These molecules are also found in the human brain and regulate multiple target proteins controlling the cellular processes in the amygdala.
The amygdala is the brain region implicated in stress-induced anxiety and is responsible for the onset of anxiety disorders, including panic attacks and post-traumatic stress disorder.
The researchers found an increased amount of one type of molecule called miR483-5p in a mouse amygdala following acute stress.
Importantly, the team showed that increased miR483-5p suppressed the expression of another gene, Pgap2, which drives changes to neuronal morphology in the brain and behavior associated with anxiety.
The researchers showed that miR-483-5p acts as a molecular brake that offsets stress-induced amygdala changes to promote anxiety relief.
Novel Pathway Discovered Through which the Brain Regulates its Response to Stress
The researchers discovered a novel amygdala miR483-5p/Pgap2 pathway through which the brain regulates its response to stress.
This discovery is the first step towards the discovery of novel, more potent and much-needed treatments for anxiety disorders that will enhance this pathway.
Dr. Valentina Mosienko, one of the study’s lead authors, said, “Stress can trigger the onset of a number of neuropsychiatric conditions that have their roots in an adverse combination of genetic and environmental factors.
While low levels of stress are counterbalanced by the natural capacity of the brain to adjust, severe or prolonged traumatic experiences can overcome the protective mechanisms of stress resilience.
This leads to the development of pathological conditions such as depression or anxiety.
Potential for the Development of Anti-Anxiety Therapies
“miRNAs are strategically poised to control complex neuropsychiatric conditions such as anxiety.
But the molecular and cellular mechanisms they use to regulate stress resilience and susceptibility were until now, largely unknown.
The miR483-5p/Pgap2 pathway we identified in this study, activation of which exerts anxiety-reducing effects, offers a huge potential for the development of anti-anxiety therapies for complex psychiatric conditions in humans.”
Conclusion
The discovery of the miR483-5p/Pgap2 pathway is a significant breakthrough in the development of anti-anxiety therapies.
This discovery offers a new drug target for anxiety disorders that have limited efficacy with currently available anti-anxiety drugs.
While the research is still in its early stages, the results are promising, and more research is needed to develop more potent treatments for anxiety disorders.
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The study was published in Nature Communications.
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