Researchers at the National Institute of Neurological Disorders and Stroke (NINDS) have discovered a new way to treat anxiety: by manipulating a specific signaling pathway in the brains of stressed young mice, they were able to effectively stop the animals’ anxious behavior. This advancement could one day lead to the development of new anti-anxiety drugs that target this pathway in humans.
NINDS Research Scientist Saurabh Pandey and Senior Research Scientist Wei Lu They spearheaded that effort. paper Published in Proceedings of the National Academy of Sciences.
About one-third One in every 10 Americans will experience an anxiety disorder at some point in their lives. These diseases include These include generalized anxiety disorder, severe phobias, panic disorder, social anxiety disorder, and post-traumatic stress disorder. These are often treated with mental health therapy and medication.
for example, Benzodiazepines is a generally effective and well-tolerated type of anti-anxiety medication, but it does have some troubling downsides: it can be addictive, interact dangerously with certain other medications, and cause a variety of side effects, including drowsiness, confusion, headaches, nausea, and tremors.
These drugs work by increasing the activity of receptors that respond to an inhibitory neurotransmitter called gamma-aminobutyric acid (GAB).GABAGABA reduces the excitability of neurons throughout the nervous system, essentially slowing down most bodily functions. This overall slowing down is also what causes the sedative effects of benzodiazepines. Some well-known brand names for these drugs include Valium, Xanax, Ativan, and Klonopin.
The NINDS team wondered if there was a better, more precise way to treat anxiety — one that didn’t cause systemic side effects. So they stressed mice until they showed telltale signs of chronic anxiety compared to their healthy, non-stressed peers. For example, the mice were less willing to explore new places, engaged in more repetitive behaviors, and avoided social interactions.
It was as if the researchers had discovered an anxiety off switch in the mouse brain.
The researchers looked for differences in the brains of anxious and non-stressed mice. They found that the levels of two neurotransmitter proteins Neuroligin 2 Anxious mice had significantly reduced levels of hormones such as GABA. Since GABA was already known for its ability to reduce anxiety, the researchers turned their attention to Neuroligin2. Further investigation revealed that chronic stress increases the activity of a protein called Src kinase, triggering a series of effects called signaling pathways that result in reduced circulating Neuroligin2. The researchers wondered whether inhibiting Src kinase activity could reduce anxiety in rodents.
To find out, Pandey, Lu and their colleagues injected anxious mice with PP2, a therapeutic drug that inhibits Src, once daily for seven days. The effect was surprising: as Src activity decreased, the corresponding signaling pathway slowed to a halt and Neuroligin2 increased. Outwardly, the animals’ anxious behavior disappeared. What’s more, there were no noticeable side effects. It was as if the researchers had found an anxiety off switch in the mouse brains.
“Reversal of anxiety-like behavior […] “This suggests a powerful mechanism for potential therapeutic applications,” the researchers commented in their paper.
Being fellow mammals, humans also have this signaling pathway, which could pave the way for the development of an entirely new class of drugs to treat anxiety, though such drugs will likely be available for several years, following further animal and clinical trials.
“We hope to further advance this research into the preclinical and clinical stages,” Lu told Big Think. “If we have the opportunity to collaborate with relevant experts from the industry, this will definitely be a future direction.”
“In principle, PP2 could be employed in tablet form, but standardization of metabolism and dosage would be the next logical step,” he adds.
The NINDS researchers aren’t the first team to study how to effectively turn off anxiety in the brain: Last year, scientists based at the University of Exeter in the UK identified a gene called Pgap2 in the amygdala of the mouse brain. Suppressing this gene reduced symptoms of anxiety in the mice.
Overall, the physical causes of anxiety disorders in the brain are still poorly understood. With the help of cutting edge technology, we may be able to essentially eliminate the anxiety that causes these disorders from the brain.
