A groundbreaking study conducted by the Molecular Cognitive Lab, led by Professor Shira Kanfo, and published in the prestigious journal Molecular Psychiatry, has unveiled a significant link between anxiety disorders and a brain receptor known as TACR3, as well as testosterone.
Anxiety is a common response to stress, but for those dealing with anxiety disorders, it can significantly impact daily life. Clinical evidence has hinted at a close connection between low testosterone levels and anxiety, particularly in men with hypogonadism, a condition characterized by reduced sexual function.
However, the precise nature of this relationship has remained unclear until now.
The study commenced with a fascinating discovery: male rodents exhibiting exceedingly high anxiety levels had notably lower levels of a specific receptor called TACR3 in their hippocampus. The hippocampus is a brain region closely associated with learning and memory processes. TACR3 is part of the tachykinin receptor family and responds to a substance known as neurokinin. This observation piqued the researchers' curiosity and
was the foundation for an in-depth investigation into the link between TACR3 deficiency, sex hormones, anxiety, and synaptic plasticity.
The rodents were classified based on their behavior in a standard elevated plus maze test measuring anxiety levels. Subsequently, their hippocampi were isolated and underwent gene expression analysis to identify genes with differential expression between rodents with extremely low anxiety and those with severe anxiety. One gene that stood out was TACR3. Previous research had revealed that mutations in genes associated with TACR3 led to a condition known as "congenital hypogonadism," resulting in reduced sex hormone production, including testosterone. Notably, young men with low testosterone often experience delayed sexual development, accompanied by depression and heightened anxiety. This led researchers to investigate the role of TACR3 in anxiety further.
Researchers successfully harnessed two innovative tools crafted in their laboratory in the study. The first, known as FORTIS, boasts the remarkable ability to detect changes in AMPA receptors within living neurons. By utilizing FORTIS, they demonstrated that inhibiting TACR3 resulted in a sharp increase in AMPA receptors on the cell surface, disrupting the parallel process of long-term synaptic strengthening, known as LTP.
The second pioneering tool employed was a novel application of cross-correlation to measure neuronal connectivity within a multi-electrode array system. This tool played a pivotal role in uncovering the profound impact of TACR3 manipulations on synaptic plasticity. Importantly, it revealed that deficiencies stemming from TACR3 inactivity could be efficiently rectified through testosterone administration, offering hope for novel approaches to address challenges related to anxiety associated with testosterone deficiency.
In conclusion, this research positions TACR3 as a central player in bridging anxiety and testosterone. The researchers have unraveled the complex mechanisms behind anxiety and opened avenues for novel therapies, including testosterone treatments, that could improve the quality of life for individuals grappling with sexual development disorders and associated anxiety and depression
