Correspondence between gene expression and neurotransmitter receptor and transporter density in the human brain
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Abstract
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.
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Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation
Tournier, J.-D., Smith, R., Raffelt, D., Tabbara, R., Dhollander, T., Pietsch, M., Christiaens, D., Jeurissen, B., Yeh, C.-H., & Connelly, A. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116137 · Cited by 2,974 · see citing works
Cell type- and brain region-resolved mouse brain proteome
Sharma, K., Schmitt, S., Bergner, C. G., Tyanova, S., Kannaiyan, N., Manrique-Hoyos, N., Kongi, K., Cantuti, L., Hanisch, U.-K., Philips, M.-A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4160 · Cited by 871 · see citing works
Canonical genetic signatures of the adult human brain
Hawrylycz, M., Miller, J. A., Menon, V., Feng, D., Dolbeare, T., Guillozet-Bongaarts, A. L., Jegga, A. G., Aronow, B. J., Lee, C.-K., Bernard, A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4171 · Cited by 663 · see citing works
Impact of regulatory variation from RNA to protein
Battle, A., Khan, Z., Wang, S. H., Mitrano, A., Ford, M. J., Pritchard, J. K., & Gilad, Y. (2015) · Science · doi:10.1126/science.1260793 · Cited by 471 · see citing works
Dynamic profiling of the protein life cycle in response to pathogens
Jovanovic, M., Rooney, M. S., Mertins, P., Przybylski, D., Chevrier, N., Satija, R., Rodriguez, E. H., Fields, A. P., Schwartz, S., Raychowdhury, R., et al. (2015) · Science · doi:10.1126/science.1259038 · Cited by 460 · see citing works
A High-Resolution<i>In Vivo</i>Atlas of the Human Brain's Serotonin System
Beliveau, V., Ganz, M., Feng, L., Ozenne, B., Højgaard, L., Fisher, P. M., Svarer, C., Greve, D. N., & Knudsen, G. M. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2830-16.2016 · Cited by 368 · see citing works
Dukart, J., Holiga, S., Rullmann, M., Lanzenberger, R., Hawkins, P. C. T., Mehta, M. A., Hesse, S., Barthel, H., Sabri, O., Jech, R., et al. (2021) · Human Brain Mapping · doi:10.1002/hbm.25244 · Cited by 347 · see citing works
Neuronal nicotinic acetylcholine receptor structure and function and response to nicotine
Dani, J. A. (2015) · International Review of Neurobiology · doi:10.1016/bs.irn.2015.07.001 · Cited by 309 · see citing works
Zilles, K. (2002) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(02)00108-6 · Cited by 244 · see citing works
Bedard, M.-A., Aghourian, M., Legault-Denis, C., Postuma, R. B., Soucy, J.-P., Gagnon, J.-F., Pelletier, A., & Montplaisir, J. (2019) · Sleep Medicine · doi:10.1016/j.sleep.2018.12.020 · Cited by 123 · see citing works
Insertion and folding pathways of single membrane proteins guided by translocases and insertases
Serdiuk, T., Steudle, A., Mari, S. A., Manioglu, S., Kaback, H. R., Kuhn, A., & Müller, D. J. (2019) · Science Advances · doi:10.1126/sciadv.aau6824 · Cited by 44 · see citing works
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Khan, A. F., Adewale, Q., Lin, S.-J., Baumeister, T. R., Zeighami, Y., Carbonell, F., Palomero-Gallagher, N., & Iturria-Medina, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-41677-w · Cited by 28 · see citing works
Self-citation
- Authors
- Hansen, J. Y., Markello, R. D., Tuominen, L., Nørgaard, M., Kuzmin, E., Palomero-Gallagher, N., Dagher, A., & Misic, B.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- University of Ottawa (CA)
- Copenhagen University Hospital (DK)
- Institut du cancer Rosalind & Morris Goodman (CA)
- Corresponding author
- Hansen, Justine Y.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 264
- Pages
- 119671
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W4302424620
- Cited by
- 69
- References
- 13
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 17 · 2023: 12 · 2022: 7
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen)
- Funders
- Canada Research Chairs
- Canada First Research Excellence Fund
- Natural Sciences and Engineering Research Council of Canada (RGPIN #017-04265)
- McGill University
- Danmarks Frie Forskningsfond (DFF-0129-00004B)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- neurotransmitter receptors, neurotransmitter transporters, receptor density, gene expression, mRNA-protein correlation, autoradiography, metabotropic receptors, 5-HT1A receptor, CB1 receptor, dopamine D2 receptor, mu-opioid receptor, genetic stability, human brain
- MeSH terms
- Autoradiography, Brain, Carrier Proteins, Humans, Gene Expression, Receptors, Neurotransmitter, Neurotransmitter Agents
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