Journal Article

Relationships between neurotransmitter receptor densities and expression levels of their corresponding genes in the human hippocampus

Forstner, Andreas J., Pelzer, Dominique I., Herms, Stefan, Cichon, Sven, Zhao, Ling, Burger, Bettina, Beins, Eva C., Hoffmann, Per, Amunts, Katrin, Mühleisen, Thomas W., Palomero-Gallagher, Nicola

2023

Overview

•Receptor density and gene expression data are from the same human hippocampal tissue.•Significant differences in receptor density only found in metabotropic receptors.•Significant differences in RNA expression mostly pertained ionotropic receptors.•Complex correlation between receptor densities and corresponding gene expressions. Neurotransmitter receptors are key molecules in signal transmission, their alterations are associated with brain dysfunction. Relationships between receptors and their corresponding genes are poorly understood, especially in humans. We combined in vitro receptor autoradiography and RNA sequencing to quantify, in the same tissue samples (7 subjects), the densities of 14 receptors and expression levels of their corresponding 43 genes in the Cornu Ammonis (CA) and dentate gyrus (DG) of human hippocampus. Significant differences in receptor densities between both structures were found only for metabotropic receptors, whereas significant differences in RNA expression levels mostly pertained ionotropic receptors. Receptor fingerprints of CA and DG differ in shapes but have similar sizes; the opposite holds true for their “RNA fingerprints”, which represent the expression levels of multiple genes in a single area. In addition, the correlation coefficients between receptor densities and corresponding gene expression levels vary widely and the mean correlation strength was weak-to-moderate. Our results suggest that receptor densities are not only controlled by corresponding RNA expression levels, but also by multiple regionally specific post-translational factors.

• Publisher: Elsevier Inc,Elsevier Limited,Academic Press,Elsevier
• Subject: Alzheimer's disease / Autopsies / Autoradiography / Brain / Dentate gyrus / Gene expression / Genomic / Hippocampus / Hippocampus - physiology / Human hippocampus / Humans / Ion channels (ligand-gated) / Metabotropic receptors / Neurotransmitter receptors / Neurotransmitters / Plastics / Post-translation / Proteins / Receptomic / Receptor density / Receptors, Neurotransmitter - genetics / Receptors, Neurotransmitter - metabolism / Regions / Ribonucleic acid / RNA / RNA - metabolism / Rna expression / Transcriptomic