Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia.
St. Petersburg University Hospital, Saint Petersburg State University, Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia.
Biomolecules. 2022 Sep 7;12(9):1259. doi: 10.3390/biom12091259.
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.
G 蛋白偶联痕量胺相关受体（TAAR）识别不同类别的胺类化合物，包括痕量胺或其他外源性和内源性分子。然而，TAAR 家族的大多数成员（TAAR2-TAAR9）被认为是参与感知先天气味的嗅觉受体。在这项研究中，在 GEO、Allen 大脑图谱和 GTEx 数据库中评估了大脑转录组数据集的 TAAR6mRNA 表达。转录组数据分析表明，TAAR6 在大脑中具有普遍的微弱 mRNA 表达，特别是在前额叶皮层和伏隔核。从伏隔核分离细胞的 RNA 测序表明，TAAR6 在某些细胞群体中的表达可能比全组织样本更为明显。奇怪的是，在伏隔核中表达 D1 和 D2 多巴胺受体的中型棘突 GABA 能神经元中，TAAR6 的表达与涉及 G 蛋白偶联受体信号转导的基因共同调节。然而，在伏隔核中的胆碱能中间神经元中，TAAR6 的表达与任何特定的生物学过程的激活无关。最后，通过 RT-PCR 分析实验验证了 TAAR6 在小鼠前额叶皮层中的表达。这些数据表明，TAAR6 在人类和小鼠大脑中低水平表达，特别是在参与精神障碍发病机制的边缘结构中，因此可能代表一个新的药物治疗靶点。
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