What is it about?
Current treatments for anxiety and depression often come with significant side effects and limited efficacy, underscoring the need for improved medications. Our research has identified a molecular chain reaction triggered by chronic stress that worsens anxiety and depression symptoms in mice. Notably, we discovered that pharmacological inhibition of a key molecule, Src kinase, using PP2, can restore balance in this signaling pathway, leading to a reduction in anxiety and depressive-like behaviors in stressed mice. This therapeutic effect hinges on the proper interaction between Myosin Va and Neuroligin2 proteins, which are essential for inhibitory synaptic transmission in the brain. These findings suggest that anxiety and depressive symptoms may be reversible at both molecular and behavioral levels, presenting a promising new target for future treatment strategies.
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Why is it important?
Persistent stress is a major contributor to the development of various neurodevelopmental and neuropsychiatric disorders. Our study uncovers a signaling pathway at inhibitory synapses in the brain that is particularly sensitive to chronic stress. Importantly, we have shown that it is possible to reverse high anxiety phenotypes in chronically stressed mice by pharmacologically targeting this signaling pathway. This discovery holds significant potential for the development of new therapeutic strategies to combat anxiety and depressive disorders.
Perspectives
We began this project during the COVID-19 pandemic, a period marked by a notable rise in anxiety and depressive symptoms among the general population. Although existing FDA-approved medications have proven effective, their side effects and limited efficacy prompted us to seek alternative drug targets for more effective treatment. Writing this article has been especially rewarding, as it brought together co-authors with whom I have had long-standing collaborations. Moreover, this work has expanded my research horizons, leading to new connections in the field of neuropsychiatric disorders and furthering my involvement in neurological disease research.
Saurabh Pandey
NINDS/NIH USA
Read the Original
This page is a summary of: Reversing anxiety by targeting a stress-responsive signaling pathway, Proceedings of the National Academy of Sciences, July 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2400078121.
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