Association of dopamine D2/3 receptor binding potential measured using PET and [11C]-(+)-PHNO with post-mortem DRD2/3 gene expression in the human brain

Komorowski, Arkadiusz; Weidenauer, Ana; Murgaš, Matej; Sauerzopf, Ulrich; Wadsak, Wolfgang; Mitterhauser, Markus; Bauer, Martin; Hacker, Marcus; Praschak-Rieder, Nicole; Kasper, Siegfried; Lanzenberger, Rupert; Willeit, Matthäus

doi:10.1016/j.neuroimage.2020.117270

Cited by 12 publications

(11 citation statements)

References 55 publications

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“…This technique, however provided great help to elucidate binding of antipsychotics to D3Rs in normal and schizophrenic subjects [48][49][50][51]. Combination of [ 11 C]-(+)-PHNO PET imaging results with brain D3R and D2R mRNA expression (taken from postmortem transcriptome atlas), in accordance with previous findings, demonstrated highest level of [ 11 C]-(+)-PHNO binding in the ventral pallidum, globus pallidus, nucleus accumbens and found strong correlation between [ 11 C]-(+)-PHNO binding and D3R mRNA but not D2R mRNA expression [52].…”

Section: D3rs In the Brain And Peripherysupporting

confidence: 89%

Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders

et al. 2021

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Dopamine (DA), as one of the major neurotransmitters in the central nervous system (CNS) and periphery, exerts its actions through five types of receptors which belong to two major subfamilies such as D1-like (i.e., D1 and D5 receptors) and D2-like (i.e., D2, D3 and D4) receptors. Dopamine D3 receptor (D3R) was cloned 30 years ago, and its distribution in the CNS and in the periphery, molecular structure, cellular signaling mechanisms have been largely explored. Involvement of D3Rs has been recognized in several CNS functions such as movement control, cognition, learning, reward, emotional regulation and social behavior. D3Rs have become a promising target of drug research and great efforts have been made to obtain high affinity ligands (selective agonists, partial agonists and antagonists) in order to elucidate D3R functions. There has been a strong drive behind the efforts to find drug-like compounds with high affinity and selectivity and various functionality for D3Rs in the hope that they would have potential treatment options in CNS diseases such as schizophrenia, drug abuse, Parkinson’s disease, depression, and restless leg syndrome. In this review, we provide an overview and update of the major aspects of research related to D3Rs: distribution in the CNS and periphery, signaling and molecular properties, the status of ligands available for D3R research (agonists, antagonists and partial agonists), behavioral functions of D3Rs, the role in neural networks, and we provide a summary on how the D3R-related drug research has been translated to human therapy.

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Section: D3rs In the Brain And Peripherysupporting

confidence: 89%

Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders

et al. 2021

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“…Since a whole-brain proteome atlas has not been published yet, spatial integration of functional imaging data relies on publicly available mRNA maps. While gene expression levels don’t necessarily reflect actual in vivo protein densities (Komorowski et al, 2020), signal alterations in fMRI studies are also impaired by confounding variables, such as network-architectures, structural and functional connectivity measures, or non-specific brain activation. To minimize BOLD signaling elicited by superimposed executive functions, control conditions need to be implemented for each paradigm, which ensures specificity of the performed tasks.…”

Section: Discussionmentioning

confidence: 99%

Regional gene expression patterns are associated with task-specific brain activation during reward and emotion processing measured with functional MRI

Komorowski

Vidal

Singh

et al. 2020

Preprint

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The exploration of the relationship between gene expression profiles and neural response patterns known to be altered in major depressive disorder provides a unique opportunity to identify novel targets for diagnosis and therapy. Here, we estimated the spatial association between genome-wide transcriptome maps and brain activation patterns from functional magnetic resonance imaging (fMRI) with two established paradigms of great relevance for mood disorders. While task-specific neural responses during emotion processing were primarily associated with expression patterns of genes involved in cellular transport, reward processing was related to neuronal development, synapse regulation, as well as gene transcription. Multimodal integration of single-site and meta-analytic imaging data with risk genes associated with depression revealed a regional susceptibility of functional activity, modulated by master regulators TCF4 and MEF2C. The identification of multiple subordinate genes correlated with fMRI maps and their corresponding regulators presumably will reshape the prospects for neuroimaging genetics.One Sentence SummaryAnalysis of the spatial association between whole-brain human gene expression and in-vivo brain activation patterns during emotion and reward processing identified TCF4 and MEF2C as master regulatory genes associated with depressive disorders.

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“…Previously, the predictive power of brain mRNA mappings of the Allen Human Brain Atlas has been investigated for several PET-derived protein expressions, including serotonin receptors (Beliveau et al, 2017; Komorowski et al, 2017; Rizzo et al, 2014), serotonin transporters (Beliveau et al, 2017; Komorowski et al, 2017), opioid receptors (Rizzo et al, 2014), dopamine receptors (Komorowski et al, 2020) and monoamine oxidase A (MAO-A) (Komorowski et al, 2017; Zanotti-Fregonara et al, 2014). The correlation coefficient ranged from −0.46 for dopamine receptor to 0.99 for glutamate receptor (Figure 4), while the mean correlation across probes and radioligands was 0.58.…”

Section: Discussionmentioning

confidence: 99%

“…The electronic search identified 164 articles from MEDLINE. After excluding conference abstracts, animal studies, non-English studies, and studies that did not meet the inclusion criteria after screening the title or abstract, 11 studies were eligible for inclusion in this study (Beliveau et al, 2017; Kim et al, 2020; Komorowski et al, 2017; Komorowski et al, 2020; Lohith et al, 2017; Norgaard et al, 2021; Pak et al, 2022; Rizzo et al, 2016; Rizzo et al, 2014; Veronese et al, 2016; Zanotti-Fregonara et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

The predictive power of mRNA mapping for Cannabinoid 1 receptor protein in the human brain

Pak

Kantonen

Pekkarinen

et al. 2022

Preprint

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Type 1 cannabinoid (CB1) receptor is expressed in cortex, hippocampus, amygdala, basal ganglia, and cerebellum. With the help of the Allen Human Brain Atlas, genomic maps visualize not only the gene expression across whole brain regions, but also the functional profile of brain structures. Therefore, it is more timely than ever to integrate genomic mapping from brain mRNA atlas with the protein expression from positron emission tomography (PET) scans for better understanding of CB1 receptor of the human brain. F18-FMPEP-d2 PET scans were retrieved from the AIVO neuroinformatics project. Autoradiography data were based on the study with H3-CP55940. mRNA expressions of CNR1 gene (Cannabinoid receptor 1) were downloaded from the Allen Human Brain Atlas. Volume of distribution (VT) from F18-FMPEP-d2 PET scans, CNR1 gene expression, and H3-CP55940 binding were calculated and Spearman correlation analysis was performed. Also, a meta-analysis was done to investigate the association between protein expression from PET and mRNA expression from the Allen Human Brain Atlas. Between VT of F18-FMPEP-d2 PET scans and CNR1 mRNA expression, moderate strength of correlation was observed (rho = 0.5026, p = 0.0354). Strong positive correlation was also found between CNR1 mRNA expression and H3-CP55940 binding (rho = 0.6727, p = 0.0281), validating the finding between F18-FMPEP-d2 PET scans and CNR1 mRNA. From the meta-analysis, the correlation coefficient ranged from −0.46 to 0.99, with a pooled effect of 0.58. In conclusion, the moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression. From the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains.HIGHLIGHTSWe investigated the association between CNR1 gene expression from the Allen Human Brain Atlas and type 1 cannabinoid (CB1) receptor expression from F18-FMPEP-d2 PET scans.The moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression.From the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains.

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Association of dopamine D2/3 receptor binding potential measured using PET and [11C]-(+)-PHNO with post-mortem DRD2/3 gene expression in the human brain

Cited by 12 publications

References 55 publications

Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders

Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders

Regional gene expression patterns are associated with task-specific brain activation during reward and emotion processing measured with functional MRI

The predictive power of mRNA mapping for Cannabinoid 1 receptor protein in the human brain

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