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

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

Author information

1
1] Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA [2] Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
2
Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
3
Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
4
1] Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA [2] Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA [3] Department of Neurosurgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
5
1] Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA [2] Department of Health Promotion & Development, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania.

Erratum in

  • J Cereb Blood Flow Metab. 2015 Jan;35(1):166.

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.

PMID:
24849661
PMCID:
PMC4126093
DOI:
10.1038/jcbfm.2014.87
[Indexed for MEDLINE]
Free PMC Article

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