Anxiety disorders are common with 1 in 4 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, leading to the onset of anxiety disorders, including panic attacks and post-traumatic stress disorder.
However, the efficacy of currently available anti-anxiety drugs is low with more than half of patients not achieving remission following treatment. Limited success in developing potent anxiolytic (anti-anxiety) drugs is a result of our poor understanding of the neural circuits underlying anxiety and molecular events resulting in stress-related neuropsychiatric states.
In this study, scientists sought to identify the molecular events in the brain that underpin anxiety. They focused on a group of molecules, known as miRNAs in animal models. This important group of molecules, also found in the human brain, regulates 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.
The discovery of a novel amygdala miR483-5p/Pgap2 pathway through which the brain regulates its response to stress is the first stepping stone towards the discovery of novel, more potent and much-needed treatments for anxiety disorders that will enhance this pathway.
Paper: 'miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala' by Mariusz Mucha et al. in Nature Communications [open access]