Naumenko V S, Osipova D V, Tsybko A S
Mol Biol (Mosk). 2010 Sep-Oct;44(5):898-903.
Selective 5-HT(1A) receptor silencer (Freud-1) is known to be one of the main factors for transcriptional regulation of brain serotonin 5-HT(1A) receptor. However, there is a lack of data on implication of Freud-1 in the mechanisms underlying genetically determined and experimentally altered 5-HT(1A) receptor system state in vivo. In the present study we have found a difference in the 5-HT(1A) gene expression in the midbrain of AKR and CBA inbred mouse strains. At the same time no distinction in Freud-1 expression was observed. We have revealed 90.3% of homology between mouse and rat 5-HT(1A) receptor DRE-element, whereas there was no difference in DRE-element sequence between AKR and CBA mice. This indicates the absence of differences in Freud-1 binding site in these mouse strains. In the model of 5-HT(1A) receptor desensitization produced by chronic 5-HT(1A) receptor agonist administration, a significant reduction of 5-HT(1A) receptor gene expression together with considerable increase of Freud-1 expression were found. These data allow us to conclude that the selective silencer of 5-HT(1A) receptor, Freud-1, is involved in the compensatory mechanisms that modulate the functional state of brain serotonin system, although it is not the only factor for 5-HT(1A) receptor transcriptional regulation.
选择性5-羟色胺（5-HT）1A受体沉默子（Freud-1）被认为是大脑5-羟色胺5-HT1A受体转录调控的主要因素之一。然而，关于Freud-1在体内基因决定和实验改变的5-HT1A受体系统状态潜在机制中的作用，目前缺乏相关数据。在本研究中，我们发现AKR和CBA近交系小鼠品系中脑5-HT1A基因表达存在差异。与此同时，未观察到Freud-1表达有区别。我们发现小鼠和大鼠5-HT1A受体DRE元件之间有90.3%的同源性，而AKR和CBA小鼠的DRE元件序列没有差异。这表明这些小鼠品系中Freud-1结合位点不存在差异。在慢性给予5-HT1A受体激动剂产生的5-HT1A受体脱敏模型中，发现5-HT1A受体基因表达显著降低，同时Freud-1表达大幅增加。这些数据使我们得出结论，5-HT1A受体的选择性沉默子Freud-1参与了调节大脑5-羟色胺系统功能状态的代偿机制，尽管它不是5-HT1A受体转录调控的唯一因素。
