Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease.
The cellular expression of dopamine D1 and D2 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 D1 and D2 mRNA-positive cells was observed compared with controls; however, the abundance of both receptor mRNAs per remaining cell was within the control range. For D2 receptor mRNA, the number of detectable D2-positive medium-sized cells decreased with increasing pathology; this decrease was accompanied by a gradual reduction in the intensity of D2 signal per cell. By contrast, for D1 receptor mRNA, despite a decrease in the number of D1 mRNA-positive cells detected, the average cellular expression of D1 mRNA was markedly reduced in the HD grade 1 case and then increased (relative to the grade 1 case) with increasing pathology, presumably reflecting the relative survival of D1-expressing striatal interneurons. The implications of these findings for providing further information on the neurodegenerative process in HD are discussed.
Augood
S J
SJ
Department of Neurobiology, Babraham Institute, Cambridge, UK.
Faull
R L
RL
Emson
P C
PC
D000368:Aged; D000369:Aged, 80 and over; D002421:Caudate Nucleus / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis* / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000235:genetics; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2