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 medium spiny 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.

TAARs as Novel Therapeutic Targets for the Treatment of Depression: A Narrative Review of the Interconnection with Monoamines and Adult Neurogenesis

“…Mutations in the taar6 gene may be associated with the severity of depression and the effectiveness of response to therapy [ 107 ]. Moreover, it turned out that TAAR5 expression in the prefrontal cortex may be impaired in patients with depression [ 108 ]. Thus, “olfactory” TAARs are of great interest for a more detailed and large-scale study in the context of mental illness.…”

“…TAAR2 was found in the lateral habenula and raphe nuclei [ 111 ]. The expression of other TAARs (most prominently TAAR5 and TAAR6) in the murine and human hippocampus and other limbic regions was also documented based on the analysis of public transcriptomic data [ 100 , 108 , 112 ]. In further studies in knockout (KO) mice, other properties of TAAR2 and TAAR5 were found that bring them closer to the pathogenesis of depression.…”

“…Perhaps the most intriguing characteristic of TAAR2-KO and TAAR5-KO mice is the increased adult neurogenesis. In both models, an increased number of neurogenic markers, namely proliferating cell nuclear antigen (PCNA), and doublecortin (DCX) in the subventricular and the subgranular zone, were found compared to wild-type [ 107 , 108 ]. Intriguingly, the expression of several TAARs including TAAR2 and TAAR5 was found during the differentiation of human pluripotent stem cells to dopaminergic neurons [ 114 ].…”

Trace Amine-Associated Receptors and Monoamine-Mediated Regulation of Insulin Secretion in Pancreatic Islets

“…Systemic transcriptomic analysis demonstrated a wide representation of TAAR5 in the adult human brain, especially in the limbic brain regions associated with the processing of olfactory signals and control of emotions [117]. A TAAR6 transcript was found in the amygdala, frontal cortex, hippocampus, striatum, and SN [2,118,119].…”