TY - JOUR
T1 - DRD2 Genotype-Based Variants Modulates D2 Receptor Distribution in Ventral Striatum
AU - Valli, Mikaeel
AU - Cho, Sang Soo
AU - Masellis, Mario
AU - Chen, Robert
AU - Rusjan, Pablo
AU - Kim, Jinhee
AU - Koshimori, Yuko
AU - Mihaescu, Alexander
AU - Strafella, Antonio P.
N1 - Funding Information:
Authors’ Contributions Study conception and design: MV and APS Data acquisition: MV and YK Data analysis: MV, SSC, and PR Data interpretation: MV and APS Manuscript drafting: MV Manuscript review and critique for important intellectual content: MV, SSC, MM, RC, PR, JK, YK, AM, and APS Approved version to be published: MV and APS Funding information Dr. Antonio Strafella was supported by the Canadian Institutes of Health Research (CIHR) (MOP 136778) and the Canada Research Chair program. Mikaeel Valli was supported by the CIHR’s Canada Graduate Scholarship, Master’s Program. Dr. Robert Chen was supported by the Catherine Manson Chair in Movement Disorders.
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/9/15
Y1 - 2019/9/15
N2 - Dopaminergic signaling within the striatum is crucial for motor planning and mental function. Neurons within the striatum contain two dopamine D2 receptor isoforms—D2 long and D2 short. The amount of expression for these receptor isoforms is affected by the genotype within two single nucleotide polymorphisms (SNPs), rs2283265 and rs1076560 (both are in high linkage disequilibrium; C > A), found in the DRD2 gene. However, it is unclear how these SNPs affect the distribution of D2 receptors in vivo within the nigrostriatal dopaminergic system. We aim to elucidate this with PET imaging in healthy young adults using [11C]-(+)-PHNO. Participants were genotyped for the DRD2 rs2283265 SNP and a total of 20 enrolled: 9 with CC, 6 with CA, and 5 with AA genotype. The main effect of genotype on [11C]-(+)-PHNO binding was tested and we found significant group effect within the ventral striatum. Specifically, CC and CA carriers had higher binding in this region compared to AA carriers. There were no observed differences between genotypes in other regions within the basal ganglia. Our preliminary results implicate that the polymorphism genotype affects the dopaminergic signaling by controlling either the quantity of D2 receptors, D2 affinity, or a combination thereof within the ventral striatum.
AB - Dopaminergic signaling within the striatum is crucial for motor planning and mental function. Neurons within the striatum contain two dopamine D2 receptor isoforms—D2 long and D2 short. The amount of expression for these receptor isoforms is affected by the genotype within two single nucleotide polymorphisms (SNPs), rs2283265 and rs1076560 (both are in high linkage disequilibrium; C > A), found in the DRD2 gene. However, it is unclear how these SNPs affect the distribution of D2 receptors in vivo within the nigrostriatal dopaminergic system. We aim to elucidate this with PET imaging in healthy young adults using [11C]-(+)-PHNO. Participants were genotyped for the DRD2 rs2283265 SNP and a total of 20 enrolled: 9 with CC, 6 with CA, and 5 with AA genotype. The main effect of genotype on [11C]-(+)-PHNO binding was tested and we found significant group effect within the ventral striatum. Specifically, CC and CA carriers had higher binding in this region compared to AA carriers. There were no observed differences between genotypes in other regions within the basal ganglia. Our preliminary results implicate that the polymorphism genotype affects the dopaminergic signaling by controlling either the quantity of D2 receptors, D2 affinity, or a combination thereof within the ventral striatum.
KW - DRD2 gene
KW - Dopamine D2 receptor
KW - Positron emission tomography
KW - Single nucleotide polymorphism
KW - [C]-(+)-PHNO radiotracer
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U2 - 10.1007/s12035-019-1543-0
DO - 10.1007/s12035-019-1543-0
M3 - Article
C2 - 30847741
AN - SCOPUS:85062714694
SN - 0893-7648
VL - 56
SP - 6512
EP - 6520
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 9
ER -