Public Transcriptomic Data Meta-Analysis Demonstrates TAAR6 Expression in the Mental Disorder-Related Brain Areas in Human and Mouse Brain.

ABSTRACT

G protein-coupled trace amine-associated receptors (TAAR) recognize different classes of amine compounds, including trace amines or other exogenous and endogenous molecules. Yet, most members of the TAAR family (TAAR2-TAAR9) are considered olfactory receptors involved in sensing innate odors. In this study, TAAR6 mRNA expression was evaluated in the brain transcriptomic datasets available in the GEO, Allen Brain Atlas, and GTEx databases. Transcriptomic data analysis demonstrated ubiquitous weak TAAR6 mRNA expression in the brain, especially in the prefrontal cortex and nucleus accumbens. RNA sequencing of isolated cells from the nucleus accumbens showed that the expression of TAAR6 in some cell populations may be more pronounced than in whole-tissue samples. Curiously, in D1 and D2 dopamine receptor-expressing medium spiny GABAergic neurons of the nucleus accumbens, TAAR6 expression was co-regulated with genes involved in G protein-coupled receptor signaling. However, in cholinergic interneurons of the nucleus accumbens, TAAR6 expression was not associated with the activation of any specific biological process. Finally, TAAR6 expression in the mouse prefrontal cortex was validated experimentally by RT-PCR analysis. These data demonstrated that TAAR6 is expressed at low levels in the human and mouse brain, particularly in limbic structures involved in the pathogenesis of mental disorders, and thus might represent a new pharmacotherapeutic target.