title: Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain.
abstract: Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT1A) and excitatory (5-HT2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (rs) in a voxel-wise and region-wise analysis. Correlations indicated a strong linear relationship between gene and protein expression for both the 5-HT1A (voxel-wise rs = 0.71; region-wise rs = 0.93) and the 5-HT2A receptor (rs = 0.66; 0.75), but only a weak association for MAO-A (rs = 0.26; 0.66) and no clear correlation for SERT (rs = 0.17; 0.29). Additionally, region-wise correlations were performed using mRNA expression from the HBT, yielding comparable results (5-HT1Ars = 0.82; 5-HT2Ars = 0.88; MAO-A rs = 0.50; SERT rs = -0.01). The SERT and MAO-A appear to be regulated in a region-specific manner across the whole brain. In contrast, the serotonin-1A and -2A receptors are presumably targeted by common posttranscriptional processes similar in all brain areas suggesting the applicability of mRNA expression as surrogate parameter for density of these proteins.
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Komorowski
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: G M
authors.initials: GM
authors.lastname: James
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Philippe
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Gryglewski
authors.affiliation: Institute of Neuroscience and Medicine (INM-2), Research Centre Jülich, 52425 Jülich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Hienert
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Spies
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Kautzky
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Vanicek
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Traub-Weidinger
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Winkler
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Wadsak
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Mitterhauser
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Hacker
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Department of Psychiatry and Pychotherapy, Division of Biological Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Lanzenberger
mesh_terms: D000328:Adult; D001344:Autopsy; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D011985:Receptors, Serotonin / Q000737:chemistry*; D059326:Serotonergic Neurons / Q000737:chemistry* / Q000473:pathology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase
keywords: 5-HT1A; 5-HT2A; MAO-A; SERT; mRNA