Regional dopamine transporter gene expression in the substantia nigra from control and Parkinson's disease brains.
OBJECTIVE
To test the hypothesis that differential regional dopamine transporter (DAT) gene expression may underlie the selective vulnerability of certain nigral dopaminergic neurons in Parkinson's disease, DAT mRNA expression was examined in neuronal subpopulations of human postmortem ventral mesencephalon from patients with Parkinson's disease and controls.


METHODS
Radioactive in situ hybridisation histochemistry using a polymerase chain reaction derived ribonucleotide probe for DAT was performed on sections of ventral mesencephalon from the brains of five donors with no history of neurological illness and from five patients with pathologically established Parkinson's disease. The number of silver grains overlying melanised neurons from the paranigral nucleus, dorsal and ventral tier, and pars lateralis of the substantia nigra pars compacta were compared with each other and to background labelling by using a one way factorial analysis of variance (ANOVA) with a significance level of 5%.


RESULTS
In control brains, there was intense DAT mRNA expression in the ventral midbrain with no significant difference in mRNA concentrations among the four regions studied. In the Parkinson's disease brains, there was an overall decrease in the intensity of DAT mRNA expression in the surviving dopaminergic neurons. There were no significant differences in signal between regions in either the control or parkinsonian brains.


CONCLUSIONS
Taken together, these findings do not support the hypothesis that differential regional DAT gene expression underlies the selective vulnerability of certain nigral dopaminergic neurons in Parkinson's disease, as the vulnerable neurons of the substantia nigra pars compacta do not express more DAT mRNA than the resistant paranigral neurons.
Neurology Service, Massachusetts General Hospital, Boston 02114, USA.
T J
TJ
Counihan
J B
JB
Penney
D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D013378:Substantia Nigra / Q000473:pathology*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015347:RNA Probes; D012333:RNA, Messenger; C493214:SLC6A3 protein, human