Discovery of natural stress-relieving pathway could help anxiety – Advanced Science News

A pathway in the brain that forms its natural stress response could be used to create new treatments for anxiety.

Up to a quarter of people globally experience anxiety and related disorders at some stage in their lives, and current treatments don’t help all patients achieve remission. Treatments include drugs that depress the central nervous system or increase levels of a chemical messenger in the brain called serotonin, which is associated with mood. However, these and other medications can have unwanted side effects and tend to treat the symptoms, not necessarily the underlying cause of the anxiety.

The problem is, we know little about what happens inside neurons during stress-induced anxiety. According to Valentina Mosienko, a neuroscientist at the University of Bristol, there are several reasons for this. Anxiety disorders are complex and are the result of changes in the expression of multiple genes in combination with the significant influence of various environmental factors including major psychological trauma, she explained.

If we better understand the brain changes that cause anxiety, new and better treatments can be developed to target these changes.

Unravel a natural pathway in the brain

To solve this problem, Mosienko and colleagues, including Robert Pawlak, chair of Functional Cell Biology at the University of Exeter, focused on examining a specific type of RNA molecule called microRNA in the brain of mice. These are small but influential molecules that can turn multiple genes on or off.

MicroRNAs are in a unique position to guide the development and progression of complex psychiatric conditions, including anxiety, as they can orchestrate the expression of different genes, Mosienko said. With so little knowledge about the role of microRNAs in regulating the stress response, the team had their work cut out. But by pinpointing the specific microRNAs activated by acute stress, the scientists hoped to decipher the key pathways that control the process that leads to anxiety.

But where in the brain should these investigations be focused? There is a group of brain structures known as the stress circuitry that work together to detect and process stress stimuli. Within this circuit is the amygdala, a brain region at the center of emotions, including fear, stress and anxiety.

This is where information from the environment is processed and stress signals are sent to other brain regions, causing the behavioral changes commonly seen in anxiety. The researchers therefore focused on this region of the amygdala to study microRNAs.

Learn from stress

Most likely evolved to improve our chances of survival, our brains have some ability to adapt to stressful conditions when a direct threat is perceived. However, severe and prolonged stress can cause more permanent adjustments, leading to anxiety.

Mariusz Mucha, lead author of the study, and Mosienko described anxiety as: [] a specific type of emotional response characterized by feelings of fear, worry, and unease, often more focused on an anticipated threat than an immediate or no threat at all.

Their study in mice shows that the brain’s response to stress is to increase a small RNA molecule called miR483-5p at the synapses, which neurons use to communicate. Synapses that receive messages form in the part of the neuron called dendritic spines, which take on a mushroom-like shape when mature.

The researchers found that increasing miR483-5p repressed the stress-associated gene, Pgap2resulting in more mature mushroom-shaped dendritic spines.

Such morphological changes drive the ability to learn that not all stressful situations are a real threat and associate the experience as unpleasant but not directly dangerous, Mucha explained. These memories last for the rest of our lives and allow us to avoid developing anxiety or anxiety-related mood disorders when facing the same stressful situation in the future.

A molecular brake

Described by researchers as a molecular brake, could treatments targeting miR483-5p amplification in the stress circuit curb anxiety?

Although the study was conducted in animals, the team is hopeful that their findings will translate to humans due to similar molecules, pathways and brain structures. Looking to the future, Mosienko says: ‘Later on, working with pharmacologists and pharmaceutical companies will enable us to find a molecule that enhances this pathway and that can be developed into an anti-anxiety drug.’

The discovery of this new amygdala pathway will pave the way for new, more powerful and much-needed treatments for anxiety disorders and, in the long run, help more people better manage their anxiety symptoms and improve their quality of life. has continued. .

Anxiety is a complex disorder that requires more studies in both animals and humans to unravel the many unknowns that remain. However, this breakthrough could be a crucial first step in the quest to fully understand the complexities of this disorder that affects so many of us.

Reference: Mariusz Mucha, Valentina Mosienko, et al., miR-483-5p compensates for the functional and behavioral effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdalaNature Communications (2023) DOI: 10.1038/s41467-023-37688-2

Featured Image: Lanju Photographs on Unsplash

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