Correlation of receptor density and mRNA expression patterns in the human cerebral cortex

Changes in distribution of associated molecular targets have been reported across several neuropsychiatric disorders. However, the high-resolution topology of most proteins is unknown and simultaneous in vivo measurement in multi-receptor systems is complicated. To account for the missing proteomic information, mRNA transcripts are typically used as a surrogate. Nonetheless, post-transcriptional and post-translational processes might cause the discrepancy between the final distribution of proteins and gene expression patterns. Therefore, this study aims to investigate ex vivo links between mRNA expression and corresponding receptor density in the human cerebral cortex. To this end, autoradiography data on the density of 15 different receptors in 38 brain regions were correlated with the expression patterns of 50 associated genes derived from microarray data (mA), RNA sequencing data (RNA-Seq) provided by the Allen Human Brain Atlas and predicted mRNA expression patterns (pred-mRNA). Spearman’s rank correlation was used to evaluate the possible links between proteomic data and mRNA expression patterns. Correlations between mRNA and protein density varied greatly between targets: Positive associations were found for e.g. the serotonin 1A (pred-mRNA: rs = 0.708; mA: rs = 0.601) or kainate receptor (pred-mRNA: rs = 0.655; mA: rs = 0.601; RNA-Seq: rs = 0.575), while most of the investigated target receptors showed low or negative correlations. The high variability in the correspondence of mRNA expression and receptor warrants caution when inferring the topology of molecular targets in the brain from transcriptome data. This highlights the longstanding value of molecular imaging data and the need for comprehensive proteomic data. ### Competing Interest Statement With relevance to this work, there is no conflict of interest to declare. R. Lanzenberger received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. Matej Murgas, Paul Michenthaler, Murray B. Reed and Gregor Gryglewski have no conflicts of interest to declare