Study links anxiety to TACR3 receptor and testosterone. Prof. Shira Knafo’s lab at Ben-Gurion University of the Negev discovered this connection and published it in Molecular Psychiatry.
Anxiety, often a stress response, can significantly affect daily life for those with anxiety disorders. Research by Prof. Knafo reveals a link between low testosterone and anxiety in men with hypogonadism. High pressure in male rodents was tied to low levels of the hippocampal receptor TACR3. This led to an in-depth study exploring the connection between TACR3 deficiency, sex hormones, anxiety, and synaptic plasticity in the brain.
Rodents were categorized based on behavior in an anxiety test. Their hippocampi were then analyzed to find genes with different expressions between low and high-anxiety groups.
One gene, TACR3, stood out in the study. Mutations in TACR3-associated genes were linked to ‘congenital hypogonadism,’ causing reduced sex hormone production, including testosterone.
Low testosterone in young men often leads to delayed sexual development, depression, and heightened anxiety. Prof. Knafo’s team used innovative tools, like FORTIS, to show that inhibiting TACR3 increased specific receptors on neuron surfaces, disrupting long-term synaptic strengthening, known as LTP.
The second tool used was a new application of cross-correlation to measure how neurons connect in a multi-electrode array system. This tool helped reveal how manipulating TACR3 profoundly affects synaptic plasticity.
Synaptic plasticity is the brain’s ability to change the strength of connections between cells. This process is crucial for the brain to adapt to the environment, allowing it to reorganize in response to new experiences.Â
Synaptic plasticity lets the brain modify connections, making neurons communicate more strongly or weakly over time. It’s a fundamental way the brain encodes and stores information, adapting to changing external and internal factors.Â
The study showed that TACR3 deficiencies could be efficiently corrected with testosterone, offering new hope for addressing anxiety linked to testosterone deficiency.
TACR3 seems to play a central role in connecting anxiety and testosterone. The research uncovered the complex mechanisms behind anxiety, suggesting potential therapies like testosterone treatments. These could improve the lives of those dealing with sexual development disorders, anxiety, and depression.
In conclusion, TACR3 emerges as a central player in bridging the gap between anxiety and testosterone. Prof. Knafo’s research not only unravels the complex mechanisms behind anxiety but also opens avenues for novel therapies, including testosterone treatments. These potential treatments could significantly improve the quality of life for individuals grappling with sexual development disorders and the associated challenges of anxiety and depression.
Journal reference:
- Wojtas, M.N., Diaz-González, M., Stavtseva, N. et al. The interplay between hippocampal TACR3 and systemic testosterone in regulating anxiety-associated synaptic plasticity. Molecular Psychiatry. DOI:10.1038/s41380-023-02361-z.