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

Synapse. 2022 Apr;76(5-6):e22226. doi: 10.1002/syn.22226. Epub 2022 Feb 13.

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 (BPND ) 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 PET-derived BPND s for DAT was intermediate (mean ρ2 = .66) with ρ2 ranging from .0811 to 1. However, the auto-correlation of mRNA expression was weak across the probes with a mean ρ2 of .09-.23. Cross-correlations between PET-derived BPND s and mRNA expression were weak with a mean ρ2 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.

Keywords: dopamine plasma membrane transport proteins; messenger RNA; positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dopamine Plasma Membrane Transport Proteins* / genetics
  • Dopamine Plasma Membrane Transport Proteins* / metabolism
  • Dopamine* / metabolism
  • Humans
  • Positron-Emission Tomography
  • Putamen / metabolism
  • RNA, Messenger / metabolism

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • RNA, Messenger
  • Dopamine