Radioligand Binding to Brain Dopamine and Serotonin Receptors and Transporters in Parkinson's Disease: Relation to Gene Polymorphisms

Abstract

ABSTRACTThe influence of variations in genes coding for dopamine and serotonin transporters and receptors on the expression of these structures in the brains of patients with Parkinson's disease (PD) is not known. In order to investigate the significance of dopamine and serotonin transporter and receptor gene polymorphisms on the expression of dopamine and serotonin transporters and the dopamine D2 and serotonin 5HT2A receptors in brain tissue in PD, we conducted a study on brain autopsy material from 16 patients diagnosed with clinical PD and 11 controls. The polymorphisms studied were DAT1 VTNR, DRD2 Taq1A, 5HTTLPR, and 5HTR2A 102 T>C, 516 C>T, His425Tyr, and Thr25Asn. Compared to control subjects, patients with PD had a significantly lowered radioligand binding to the dopamine transporter (DAT) in nucleus caudatus (p = .001) and putamen (p = .008), and to the serotonin transporter in gyrus cingulatus (p = .010) and nucleus caudatus (p = .032). We did not observe any significant associations between genetic polymorphisms and the extent of radioligand binding or between the polymorphisms and a diagnosis of PD. In conclusion, the density of brain dopamine and serotonin transporters in patients with PD was reduced. However, there were no associations between the investigated genotypes and the expression of the corresponding receptors and transporters.