Correspondence between gene expression and neurotransmitter receptor and transporter density in the human brain
Authors: Hansen JY, Markello RD, Tuominen L, Nørgaard M, Kuzmin E, Palomero-Gallagher N, Dagher A, Misic B
Affiliations
1 McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Canada. Electronic address: justine.hansen@mail.mcgill.ca.
2 McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Canada.
3 Department of Psychiatry, The Royal's Institute of Mental Health Research, University of Ottawa, ON, Canada.
4 Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Copenhagen, Denmark; Center for Reproducible Neuroscience, Department of Psychology, Stanford University, Stanford, California, USA.
5 Department of Biology, Centre for Applied Synthetic Biology, Concordia University, Montréal, Canada; Department of Human Genetics, Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Canada.
6 Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH, Aachen, Germany; C. and O. Vogt Institute for Brain Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
7 McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Canada. Electronic address: bratislav.misic@mcgill.ca.
Description
Neurotransmitter receptors modulate signaling between neurons. Thus, neurotransmitter receptors and transporters play a key role in shaping brain function. Due to the lack of comprehensive neurotransmitter receptor/transporter density datasets, microarray gene expression measuring mRNA transcripts is often used as a proxy for receptor densities. In the present report, we comprehensively test the spatial correlation between gene expression and protein density for a total of 27 neurotransmitter receptors, receptor binding-sites, and transporters across 9 different neurotransmitter systems, using both PET and autoradiography radioligand-based imaging modalities. We find poor spatial correspondences between gene expression and density for all neurotransmitter receptors and transporters except four single-protein metabotropic receptors (5-HT1A, CB1, D2, and MOR). These expression-density associations are related to gene differential stability and can vary between cortical and subcortical structures. Altogether, we recommend using direct measures of receptor and transporter density when relating neurotransmitter systems to brain structure and function.
Links
PubMed: https://pubmed.ncbi.nlm.nih.gov/36209794/
DOI: 10.1016/j.neuroimage.2022.119671