Dopamine D-1 and D-2 receptor gene expression in the striatum in Huntington's disease

The cellular expression of dopamine D-1 and D-2 receptor mRNAs was investigated in the postmortem human caudate nucleus of control cases and genetically and pathologically confirmed cases of Huntington's disease (HD) by using quantitative in situ hybridization. The HD cases were categorized (0-4) by severity of striatal neuropathology according to the Vonsattel scale. For the HD grade 0 case, a pronounced reduction in the number of D-1 and D-2 mRNA-positive cells was observed compared with controls; however, the abundance of both receptor mRNAs per remaining cell was within the control range. For D-2 receptor mRNA, the number of detectable D-2-positive medium-sized cells decreased with increasing pathology; this decrease was accompanied by a gradual reduction in the intensity of D-1 signal per cell. By contrast, for D-1 receptor mRNA, despite a decrease in the number of D-1 mRNA-positive cells detected, the average cellular expression of D-1 mRNA was markedly reduced in the HD grade I case and then increased (relative to the grade I case) with increasing pathology, presumably reflecting the relative survival of D-1-expressing striatal interneurons. The implications of these findings for providing further information on the neurodegenerative process in HD are discussed.