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Interplay between hippocampal TACR3 and systemic testosterone in regulating anxiety-associated synaptic plasticity.
Magdalena Natalia Wojtas1,2, Marta Diaz-González1, Nadezhda Stavtseva1
1Department of Physiology and Cell Biology, The National Institute for Biotechnology in the Negev, and the School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Molecular Psychiatry
|December 22, 2023
Summary
Tachykinin receptor 3 (TACR3) dampens anxiety by influencing synaptic plasticity and sex hormones. TACR3 dysfunction impairs long-term potentiation and alters neuronal connectivity, highlighting its role in anxiety disorders.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Tachykinin receptor 3 (TACR3) is a G protein-coupled receptor activated by neurokinin B (NKB).
- TACR3 dysfunction is linked to pubertal failure and anxiety, but underlying mechanisms are unclear.
- Investigating TACR3's role in anxiety, sex hormones, and synaptic plasticity is crucial.
Purpose of the Study:
- To explore the relationship between TACR3 expression, anxiety levels, sex hormones, and synaptic plasticity in a rat model.
- To elucidate the impact of TACR3 modulation on neuronal function and anxiety-related behaviors.
Main Methods:
- Utilized a rat model to assess TACR3 expression in the ventral hippocampus.
- Measured TACR3 fluctuations during the estrous cycle and in response to sex hormones.
- Employed multielectrode arrays and biochemical analyses to study synaptic plasticity, including CaMKII and AMPA receptor phosphorylation, spine density, and long-term potentiation (LTP).
Main Results:
- Severe anxiety correlated with reduced TACR3 expression in the ventral hippocampus.
- TACR3 expression varied with the estrous cycle in females and increased with testosterone during sexual development in males, reducing anxiety.
- TACR3 inhibition enhanced synaptic activity, increased spine density, and altered neuronal firing patterns; deficient TACR3 impaired LTP and was linked to lower testosterone, effects partially reversed by testosterone treatment.
Conclusions:
- TACR3 plays a significant role in regulating anxiety, sex hormones, and synaptic plasticity.
- Aberrant TACR3 expression impacts neuronal structure and function, affecting anxiety-related behaviors.
- Findings suggest TACR3 and its pathways as potential therapeutic targets for anxiety disorders associated with TACR3 dysfunction.
