Vaganova Anastasia N, Fesenko Zoia S, Volnova Anna B, Gainetdinov Raul R
Institute of Translational Biomedicine, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia.
Biomolecules. 2025 Aug 3;15(8):1117. doi: 10.3390/biom15081117.
Dopamine transporter (DAT) mutations are associated with neurological and psychiatric diseases, and DAT gene knockout in rats (DAT-KO) provides an opportunity to evaluate the DAT role in pathological conditions. We analyzed DAT expression and co-expression with other genes in the substantia nigra and striatum in public transcriptomic data represented in the GEO repository and then estimated the identified DAT co-expression pattern in DAT-KO rats by RT-PCR. In silico analysis confirmed DAT expression in the substantia nigra and absence of DAT mRNA in the striatum. Also, DAT is co-expressed with genes involved in dopamine signaling, but these associations are disrupted in dopamine neuron-damaging conditions. To estimate this co-expression pattern when DAT expression is lost, we evaluate it in the substantia nigra of DAT-KO rats. However, in DAT-KO rats the associations between genes involved in dopamine signaling were not disturbed compared to wild-type littermates, and tyrosine hydroxylase expression upregulation in the substantia nigra of these animals may be considered as compensation for the loss of dopamine reuptake. Further studies of expression regulation in dopamine neurons of DAT-KO rats may provide valuable information for compensatory mechanisms in substantia nigra dopaminergic neurons.
多巴胺转运体(DAT)突变与神经和精神疾病相关,大鼠多巴胺转运体基因敲除(DAT-KO)为评估DAT在病理状态下的作用提供了契机。我们在GEO数据库中所呈现的公开转录组数据中,分析了黑质和纹状体中DAT的表达及其与其他基因的共表达情况,随后通过逆转录-聚合酶链反应(RT-PCR)评估了DAT-KO大鼠中所识别出的DAT共表达模式。计算机分析证实了黑质中DAT的表达以及纹状体中DAT信使核糖核酸(mRNA)的缺失。此外,DAT与参与多巴胺信号传导的基因共表达,但在多巴胺神经元受损的情况下,这些关联会被破坏。为了评估DAT表达缺失时的这种共表达模式,我们在DAT-KO大鼠的黑质中进行了评估。然而,与野生型同窝仔鼠相比,DAT-KO大鼠中参与多巴胺信号传导的基因之间的关联并未受到干扰,这些动物黑质中酪氨酸羟化酶表达上调可被视为对多巴胺再摄取丧失的一种补偿。对DAT-KO大鼠多巴胺神经元中表达调控的进一步研究,可能为黑质多巴胺能神经元的代偿机制提供有价值的信息。