Researchers Discover a New Neurotransmitter System in The Brain: Trace Amine-Associated Receptor 5 (TAAR5)

Date: November 10, 2020 Neuropharmacology

Fig.1 TAAR5 is not only present in the olfactory system, but also in the part of the brain responsible for emotions

Research Highlights

• GPCR TAARs can sense the decarboxylation products of biogenic amines and amino acids.
• The number of dopamine neurons in TAAR5 knockout mice increased.
• TAAR5 is expressed in neurogenic areas and periventricular areas.
• TAAR5 gene knockout mice show increased adult neurogenesis.

Researchers have discovered a new type of neurotransmitter system in the brain. The system transmits innate olfactory information to brain regions related to emotional processing through the trace amine-related receptor 5 (TAAR5) receptor. The results of the study, published in "Neuropharmacology", may provide new treatment opportunities for neurodegenerative diseases such as depression, Parkinson's disease and schizophrenia.

Trace amine-associated receptors (TAARs) are a class of sensory G protein-coupled receptors

Trace amine-related receptors (TAARs) are a class of sensory G protein-coupled receptors that can detect biogenic amines (amino acid decarboxylation products). Most TAARs (TAAR2-TAAR9) are mainly described in the olfactory epithelium, and are considered to be olfactory receptors that sense the pre-weather odor (decayed tissue, pheromone, predator). However, scientists have found that TAARs also exist in certain brain regions and is involved in the regulation of our emotions. Recent evidence indicates that one of the members of this family, TAAR5, is also projected by the olfactory system and expressed in the limbic brain area involved in emotion regulation, and exhibits anxiolytic behavior and changes in brain serotonin transmission.

In this study, the research team characterized a mouse line lacking TAAR5 (TAAR5 knockout, TAAR5-KO mice), which expresses β-galactosidase-mapped TAAR5 expression. They found that TAAR5 knockout mice with the "off" gene encoding the TAAR5 protein showed antidepressant effects, and showed anxiolytic behavior and changes in brain serotonin transmission.

Further detailed research focuses on how TAAR5 affects dopamine neurons in the substantia nigra of the brain. The loss of dopamine neurons is associated with certain neurodegenerative diseases, including Parkinson's disease. They found that in TAAR5-KO mice, the number of dopamine neurons increased, indicating a potential increase in the proliferation of dopamine neurons.

Furthermore, the analysis of the expression of TAAR5β-galactosidase showed that TAAR5 is present in the main neurogenic areas of the brain, such as the subventricular zone (SVZ), subgranular zone (SGZ) and potential nerves with fewer features around the third ventricle Source area.

These observations indicate that TAAR5 is not only involved in the regulation of emotional states, but also involved in adult neurogenesis and dopamine transmission. Therefore, future TAAR5 antagonists can not only exert antidepressant and/or anxiolytic effects, but also provide new treatment opportunities for neurodegenerative diseases such as Parkinson's disease.

The work has been published in the journal Frontiers in Molecular Neuroscience.

1. Story Source: Efimova, E. V., Kozlova, A. A., Razenkova, V., Katolikova, N. V., Antonova, K. A., Sotnikova, T. D., ... & Musienko, P. E. (2020). Increased dopamine transmission and adult neurogenesis in trace amine-associated receptor 5 (TAAR5) knockout mice. Neuropharmacology, 182, 108373. DOI: 10.1016/j.neuropharm.2020.108373
2. More Information: Espinoza, S., Sukhanov, I., Efimova, E. V., Kozlova, A., Antonova, K. A., Illiano, P., ... & Rocchi, A. (2020). Trace Amine-Associated Receptor 5 Provides Olfactory Input Into Limbic Brain Areas and Modulates Emotional Behaviors and Serotonin Transmission. Frontiers in Molecular Neuroscience, 13, 18.

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