Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain

<span class="paragraphSection"><div class="boxTitle">Abstract</div>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-HT_1A) and excitatory (5-HT_2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (<span style="font-style:italic;">r</span>_s) in a voxel-wise and region-wise analysis. Correlations indicated a strong linear relationship between gene and protein expression for both the 5-HT_1A (voxel-wise <span style="font-style:italic;">r</span>_s = 0.71; region-wise <span style="font-style:italic;">r</span>_s = 0.93) and the 5-HT_2A receptor (<span style="font-style:italic;">r</span>_s = 0.66; 0.75), but only a weak association for MAO-A (<span style="font-style:italic;">r</span>_s = 0.26; 0.66) and no clear correlation for SERT (<span style="font-style:italic;">r</span>_s = 0.17; 0.29). Additionally, region-wise correlations were performed using mRNA expression from the HBT, yielding comparable results (5-HT_1A<span style="font-style:italic;">r</span>_s = 0.82; 5-HT_2A<span style="font-style:italic;">r</span>_s = 0.88; MAO-A <span style="font-style:italic;">r</span>_s = 0.50; SERT <span style="font-style:italic;">r</span>_s = −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.</span>

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