Listen to this article Scientists discover brain gene that can inhibit anxiety
New study discovers brain gene that can reduce anxiety
An international team of scientists led by researchers from the Universities of Bristol and Exeter has identified a gene in the brain that drives anxiety symptoms. The team found that modifying the gene can reduce anxiety levels, offering a promising new drug target for anxiety disorders. The study was published online in Nature Communications on April 25, 2023.
Anxiety disorders are common, with 1 in 4 people being diagnosed with a disorder at least once in their lifetime. Severe psychological trauma can trigger genetic, biochemical and morphological changes in neurons in the amygdala, the brain region implicated in stress-induced anxiety. This can lead to the onset of anxiety disorders, including panic attacks and post-traumatic stress disorder.
Current Treatment Limitations
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 drugs is due to our poor understanding of the neural circuits underlying anxiety and molecular events resulting in stress-related neuropsychiatric states.
In this study, the scientists 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 behavior associated with anxiety.
New Drug Target
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 a promising first step towards the development of novel, more potent, and much-needed treatments for anxiety disorders that enhance this pathway.
Potential for Anti-Anxiety Therapies
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: “Stress can trigger the onset of a number of neuropsychiatric conditions that have their roots in an adverse combination of genetic and environmental factors.
The natural capacity of the brain can balance low levels of stress, but severe or prolonged traumatic experiences can overcome stress resilience’s protective mechanisms, which leads to the development of pathological conditions like anxiety or depression. miRNAs can control complex neuropsychiatric conditions such as anxiety strategically.
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 huge potential for the development of anti-anxiety therapies for complex psychiatric conditions in humans.”
The Medical Research Council, Academy of Medical Sciences, Leverhulme Trust, Marie Sklodowska-Curie, and the Polish National Science Centre provided funding for the research.
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