Coexpression of Gene Transcripts with Monoamine Oxidase A Quantified by Human In Vivo Positron Emission Tomography. (25th December 2021)

• Record Type: Journal Article
• Authors: Godbersen, G M; Murgaš, M; Gryglewski, G; Klöbl, M; Unterholzner, J; Rischka, L; Spies, M; Baldinger-Melich, P; Winkler, D; Lanzenberger, R
• Is Part Of: Cerebral cortex. Volume 32:Number 16(2022)
• Page Start: 3516
• Page End: 3524
• Publication Date: 2021-12-25
• Subjects: Allen Human Brain Atlas -- antidepressant -- MAO-A -- molecular neuroimaging -- transcriptomics; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhab430
• Languages: English
• ISSNs: 1047-3211

Abstract

Abstract: 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 [ 11 C]harmine positron emission tomography scans. Coexpression analysis was based on Spearman's ρ, 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 (ρ = 0.08) while correlation was found in subcortical areas (ρ = 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.