TY - JOUR
T1 - Correspondence between gene expression and neurotransmitter receptor and transporter density in the human brain
AU - Hansen, Justine Y
AU - Markello, Ross D
AU - Tuominen, Lauri
AU - Nørgaard, Martin
AU - Kuzmin, Elena
AU - Palomero-Gallagher, Nicola
AU - Dagher, Alain
AU - Misic, Bratislav
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - Humans
KW - Receptors, Neurotransmitter/genetics
KW - Brain/diagnostic imaging
KW - Autoradiography
KW - Neurotransmitter Agents/metabolism
KW - Carrier Proteins/metabolism
KW - Gene Expression
UR - http://www.scopus.com/inward/record.url?scp=85139853086&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2022.119671
DO - 10.1016/j.neuroimage.2022.119671
M3 - Journal article
C2 - 36209794
SN - 1053-8119
VL - 264
SP - 1
EP - 11
JO - NeuroImage
JF - NeuroImage
M1 - 119671
ER -