Coexpression of Gene Transcripts with Monoamine Oxidase A Quantified by Human In Vivo Positron Emission Tomography

The monoamine oxidase A (MAO-A) is integral to monoamine metabolism and is thus relevant to the pathophysiology of various neuropsychiatric disorders; however, associated gene-enzyme relations are not well understood. This study aimed to unveil genes coexpressed with MAO-A. Therefore, 18 179 mRNA expression maps (based on the Allen Human Brain Atlas) were correlated with the cerebral distribution volume (V-T) of MAO-A assessed in 36 healthy subjects (mean age +/- standard deviation: 32.9 +/- 8.8 years, 18 female) using [C-11]harmine positron emission tomography scans. Coexpression analysis was based on Spearman's rho, over-representation tests on Fisher's exact test with false discovery rate (FDR) correction. The analysis revealed 35 genes in cortex (including B-cell translocation gene family, member 3, implicated in neuroinflammation) and 247 genes in subcortex (including kallikrein-related peptidase 10, implicated in Alzheimer's disease). Significantly over-represented Gene Ontology terms included neuron development, neuron differentiation, and cell-cell signaling as well as axon and neuron projection. In vivo MAO-A enzyme distribution and MAOA expression did not correlate in cortical areas (rho = 0.08) while correlation was found in subcortical areas (rho = 0.52), suggesting influences of region-specific post-transcriptional and -translational modifications. The herein reported information could contribute to guide future genetic studies, deepen the understanding of associated pathomechanisms and assist in the pursuit of novel therapeutic targets.

Automated summary

The study identified multiple genes coexpressed with MAO-A, including those playing important roles in neuroinflammation and Alzheimer's disease. Differential gene expression was found between the cortical and subcortical regions of the brain, potentially due to region-specific post-transcriptional and translational modifications.