The influence of genetic variants on striatal dopamine transporter and D2 receptor binding after TBI

J Cereb Blood Flow Metab. 2014 Aug;34(8):1328-39. doi: 10.1038/jcbfm.2014.87. Epub 2014 May 21.

Abstract

Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [(11)C]βCFT and [(11)C]raclopride. We examined subjects with moderate/severe TBI (N=12) ∼1 year post injury and similarly matched healthy controls (N=13). The variable number of tandem repeat polymorphism within the DAT gene and the TaqI restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Brain Injuries / diagnostic imaging
  • Brain Injuries / genetics*
  • Brain Injuries / metabolism
  • Case-Control Studies
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / metabolism
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Glasgow Coma Scale
  • Humans
  • Magnetic Resonance Imaging
  • Multivariate Analysis
  • Polymorphism, Restriction Fragment Length*
  • Positron-Emission Tomography
  • Protein Binding
  • Putamen / diagnostic imaging
  • Putamen / metabolism
  • Receptors, Dopamine D2 / genetics*
  • Tandem Repeat Sequences / genetics

Substances

  • DRD2 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • Dopamine