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

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Neuropsychiatric disorders involve altered molecular targets, but protein topology is often unknown.
• Messenger ribonucleic acid (mRNA) is used as a surrogate for protein distribution, but post-transcriptional/translational changes can cause discrepancies.
• Simultaneous in vivo measurement in multi-receptor systems is challenging.

Purpose of the Study:

• To investigate ex vivo links between mRNA expression and corresponding receptor density in the human cerebral cortex.
• To evaluate the correlation between gene expression patterns and protein distribution using multiple data sources.

Main Methods:

• Correlated autoradiography data (15 receptors, 38 brain regions) with mRNA expression patterns from microarray (mA), RNA sequencing (RNA-Seq), and predicted mRNA (pred-mRNA).
• Utilized Spearman's rank correlation to assess links between proteomic data and mRNA expression patterns.
• Analyzed data from the Allen Human Brain Atlas.

Main Results:

• Correlations between mRNA and protein density varied significantly across targets.
• Positive associations were observed for serotonin 1A and kainate receptors.
• Negative associations were found for GABA A receptor subunits α3 and α5.
• Most other investigated receptors showed low correlations between mRNA and protein density.

Conclusions:

• The high variability in mRNA expression and receptor spatial distribution correspondence necessitates caution when inferring brain molecular target topology from transcriptome data.
• Highlights the value of molecular imaging and the need for comprehensive proteomic studies.
• Transcriptome data alone may not be sufficient for accurate brain receptor mapping.