Open access post mortem transcriptome atlases such as the Allen Human Brain Atlas (AHBA) can inform us about mRNA expression of numerous proteins of interest across the whole brain, while in vivo protein binding in the human brain can be quantified by means of neuroreceptor positron emission tomography (PET). By combining both modalities, the association between regional gene expression and receptor distribution in the living human brain can be approximated. Here, we compare the characteristics of D2 and D3 dopamine receptor distribution by applying the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and mRNA expression data from the AHBA. Since [11C]-(+)-PHNO has a higher affinity for D3 compared to D2 receptors, we hypothesized that there is a stronger relationship between D2/3 non-displaceable binding potentials (BPND) and D3 mRNA expression. To investigate the relationship between D2/3 BPND and mRNA expression of dopamine D2 and D3 receptors we performed [11C]-(+)-PHNO PET scans in 27 healthy subjects (12 females) and extracted D2 and D3 mRNA expression data from the AHBA. We also calculated D2/D3 mRNA expression ratios to imitate the mixed D2/3 signal of [11C]-(+)-PHNO. In accordance with our a priori hypothesis, strong correlations between the [11C]-(+)-PHNO and D3 mRNA expression signal were found. However, there was no significant correlation with D2 mRNA expression. Calculated D2/D3 mRNA expression ratios also showed a positive correlation with [11C]-(+)-PHNO binding, reflecting the mixed D2/3 signal of the radioligand. Our study supports the usefulness of combining mRNA expression data from open access brain atlases with in vivo imaging data in order to gain more detailed knowledge on neurotransmitter signaling.

中文翻译：

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使用 PET 和 [11C]-(+)-PHNO 测量的多巴胺 D2/3 受体结合电位与人脑中死后 DR2/3 基因表达的关联

开放获取的死后转录组图谱，例如艾伦人脑图谱 (AHBA)，可以让我们了解整个大脑中众多感兴趣蛋白质的 mRNA 表达，而人脑中的体内蛋白质结合可以通过神经受体正电子发射来量化断层扫描（PET）。通过结合这两种模式，可以近似估计活人大脑中区域基因表达和受体分布之间的关联。在这里，我们通过应用多巴胺 D2/3 受体激动剂放射性配体 [11C]-(+)-PHNO 和来自 AHBA 的 mRNA 表达数据来比较 D2 和 D3 多巴胺受体分布的特征。由于与 D2 受体相比，[11C]-(+)-PHNO 对 D3 具有更高的亲和力，因此我们假设 D2/3 不可置换结合电位 (BPND) 和 D3 mRNA 表达之间存在更强的关系。为了研究 D2/3 BPND 与多巴胺 D2 和 D3 受体 mRNA 表达之间的关系，我们对 27 名健康受试者（12 名女性）进行了 [11C]-(+)-PHNO PET 扫描，并从 AHBA 中提取了 D2 和 D3 mRNA 表达数据。我们还计算了 D2/D3 mRNA 表达比，以模拟 [11C]-(+)-PHNO 的混合 D2/3 信号。根据我们的先验假设，发现 [11C]-(+)-PHNO 和 D3 mRNA 表达信号之间存在很强的相关性。然而，与D2 mRNA表达没有显着相关性。计算的 D2/D3 mRNA 表达比也显示与 [11C]-(+)-PHNO 结合呈正相关，反映了放射性配体的混合 D2/3 信号。我们的研究支持将开放获取脑图谱的 mRNA 表达数据与体内成像数据相结合的有用性，以获得有关神经递质信号传导的更详细的知识。