About one in four adults will be diagnosed with an anxiety issue at some point during their lifetime, but treating anxiety is still challenging. It's estimated that about half of anxiety patients don't get relief from the drugs that are currently available to treat the disorder. But new research may help change that. Scientists have identified a gene that seems to have a major influence on anxiety. When the expression of this gene is reduced, anxiety levels drop in a mouse model of anxiety caused by stress. The findings have been reported in Nature Communications.
Severe episodes of stress or trauma can lead to a variety of changes in a region of the brain called the amygdala. In previous work, the amygdala has been connected with anxiety disorders such as post-traumatic stress disorder and panic attacks. Stress causes changes in amygdala circuitry and gene expression.
In this work, the researchers examined microRNAs in animal models of anxiety, as they searched for the biochemical mechanisms that underlie the disorder. Previous work has shown that miRNAs can affect a variety of proteins that are crucial to amygdala cell function. MicroRNAs are small molecules that are transcribed from the genome but do not encode for protein. They can regulate protein activity.
After an episode of acute stress, the researchers determined that the level of an miRNA called miR483-5p was increased in the mouse amygdala. Higher miR483-5p levels were found to reduce the expression of a gene called Pgap2, which affects the structure of neurons in the brain and anxiety behaviors. The investigators determined that miR-483-5p can stop the biochemical processes that are related to changes in the amygdala caused by acute stress. This miRNA could open up new avenues for anxiety treatments as well.
Because of genetic or environmental factors, stress may lead to a variety of neuropsychiatric conditions in some individuals. The brain can often cope with low levels of stress, but when stress is prolonged or particularly traumatic, those coping mechanisms may break down, causing conditions like anxiety or depression, explained co-corresponding study author Dr. Valentina Mosienko of the University of Bristol.
“miRNAs are strategically poised to control complex neuropsychiatric conditions such as anxiety," noted Mosienko. "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.”
Sources: University of Bristol, Nature Communications