Limited power of dopamine transporter mRNA mapping for predicting dopamine transporter availability

Abstract

Dopamine transporters (DAT) are transmembrane proteins that translocate dopamine from the extracellular space into presynaptic neurons. We aimed to investigate the predictive power of DAT mRNA for DAT protein expression, measured using positron emission tomography (PET). We performed 18 F-FP-CIT PET scans in 35 healthy individuals. Binding potentials (BP ND ) from the ventral striatum, caudate nucleus, putamen, and middle frontal, orbitofrontal, cingulate, parietal, and temporal cortices were measured. DAT gene expression data were obtained from the freely available Allen Human Brain Atlas derived from six healthy donors. The auto-correlation of PETderived BP ND s for DAT was intermediate (mean ρ 2 = .66) with ρ 2 ranging from .0811 to 1. However, the auto-correlation of mRNA expression was weak across the probes with a mean ρ 2 of .09-.23. Cross-correlations between PET-derived BP ND s and mRNA expression were weak with a mean ρ 2 ranging from 0 to .22 across the probes. In conclusion, we observed weak associations between DAT mRNA expression and DAT availability in human brains. Therefore, DAT mRNA mapping may have only limited predictive power for DAT availability in humans. However, the difference in distribution of DAT mRNA and DAT protein may influence this limitation.

Patient-specific multi-modal modeling uncovers neurotransmitter receptor involvement in motor and non-motor axes of Parkinson’s disease

“…Although receptor densities and gene expression are correlated for selected receptor subunit genes and across certain cytoarchitectonically-defined regions [39], this is not universally true [40]. Low correlations are also observed between gene expression and in vivo PET imaging of dopamine transporters [41]. On the other hand, our averaged receptor templates are correlated with neurobiological processes such as drug-induced cerebral blood flow changes [42].…”

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

“…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).…”

“…Previous studies have proved the predictive power of brain mRNA mapping for in vivo protein expression from positron emission tomography (PET) for serotonin receptors (Beliveau et al, 2017; Komorowski et al, 2017; Rizzo et al, 2014), opioid receptors (Rizzo et al, 2014) and monoamine oxidase A (Komorowski et al, 2017; Zanotti-Fregonara et al, 2014), based on the key assumption that mRNA expression predicts protein expression. However, the studies on serotonin transporter or dopamine transporter showed a weak association between mRNA and protein levels, emphasizing the role of translational and post-translational mechanisms (Beliveau et al, 2017; Pak et al, 2022). To date there have been no published data on the association of CB1 gene expression with CB1 protein expression in humans.…”

Association of CNR1 gene and cannabinoid 1 receptor protein in the human brain

“…However, the studies on serotonin transporter or dopamine transporter showed a weak association between mRNA and protein levels, emphasizing the role of translational and post-translational mechanisms (Beliveau et al, 2017;Pak et al, 2022). To date, there have been no published data on the association of CB1 gene expression with CB1 protein expression in humans.…”

“…Previous studies have proved the predictive power of brain mRNA mapping for in vivo protein expression from positron emission tomography (PET) for serotonin receptors (Beliveau et al, 2017; Komorowski et al, 2017; Rizzo et al, 2014), opioid receptors (Rizzo et al, 2014), and monoamine oxidase A (Komorowski et al, 2017; Zanotti‐Fregonara et al, 2014), based on the key assumption that mRNA expression predicts protein expression. However, the studies on serotonin transporter or dopamine transporter showed a weak association between mRNA and protein levels, emphasizing the role of translational and post‐translational mechanisms (Beliveau et al, 2017; Pak et al, 2022). To date, there have been no published data on the association of CB1 gene expression with CB1 protein expression in humans.…”