A team of scientists have discovered that modification of a gene in the brain can reduce anxiety levels, offering an exciting novel drug target for anxiety disorders.
The discovery, led by researchers at the Universities of Bristol and Exeter in the UK, is published in Nature Communications.
Anxiety disorders are common, with one in four people diagnosed with a disorder at least once in their lifetime. Severe psychological trauma can trigger genetic, biochemical and morphological changes in neurons in the brain’s amygdala – the brain region implicated in stress-induced anxiety.
However, the efficacy of currently available anti-anxiety drugs is low, with more than half of patients not achieving remission following treatment.
In this study, scientists sought to identify the molecular events in the brain that underpin anxiety. They focused on miRNAs, which regulate multiple target proteins controlling the cellular processes in the amygdala.
Following acute stress, the team found an increased amount of one type of molecule called miR483-5p in a mouse amygdala. Importantly, the team showed that increased miR483-5p suppressed the expression of another gene, Pgap2, which in turn drives changes to neuronal morphology in the brain and behaviour associated with anxiety.
Together, the researchers showed that miR-483-5p acts as a molecular brake that offsets stress-induced amygdala changes to promote anxiety relief.
This is the first step towards the discovery of novel, more potent and much-needed treatments for anxiety disorders that will enhance this pathway.
The miR483-5p/Pgap2 pathway
Dr Valentina Mosienko, one of the study’s lead authors and an MRC Fellow and Lecturer in Neuroscience in Bristol’s School of Physiology, Pharmacology and Neuroscience, said: “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, leading to the development of pathological conditions such as depression or anxiety.
“miRNAs are strategically poised to control complex neuropsychiatric conditions such as anxiety. 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.”
