Interplay between hippocampal TACR3 and systemic testosterone in regulating anxiety-associated synaptic plasticity

Authors: Magdalena Natalia Wojtas, Marta Diaz-González, Nadezhda Stavtseva, Yuval Shoam, Poonam Verma, Assaf Buberman, Inbar Izhak, Aria Geva, Roi Basch, Alberto Ouro, Lucia Perez-Benitez, Uri Levy, Erika Borcel, Ángel Nuñez, Cesar Venero, Noa Rotem-Dai, Isana Veksler-Lublinsky and Shira Knafo

Molecular Psychiatry, 22 December 2023

Scientists use Axion’s noninvasive Maestro MEA to explore the impact of testosterone in the brain.

Links between abnormal testosterone levels and mental health disorders including anxiety, depression, and schizophrenia are well documented but the underlying mechanisms are not fully understood. In this study, scientists use a rat model to explore the complex relationship between sex hormones, anxiety, synaptic plasticity, and hippocampal tachykinin receptor 3 (TACR3) expression. Overall, the authors found that TACR3 plays a key role as a “critical mediator between testosterone levels and anxiety-like behavior,” and note as well “the modulatory effect of sex hormones on TACR3 expression and its reciprocal control over sex hormone levels and anxiety-like behavior.” Using Axion’s noninvasive Maestro microelectrode array (MEA) platform, the researchers also demonstrated that altered TACR3 activity impairs neuronal connectivity and long-term potentiation in hippocampal neurons. Testosterone treatment rescued neurons with dysfunctional TACR3, suggesting a potential therapeutic pathway for some people with anxiety disorders.