Markers for dopaminergic neurotransmission in the cerebellum in normal individuals and patients with Parkinson's disease examined by RT-PCR.
The presence of neuronal elements that are indicative of dopaminergic neurotransmission in cerebellum suggest that this brain region may contribute to the motor symptoms or dyskinesia seen in Parkinson's disease. Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of markers for dopaminergic neurotransmission in the cerebellum from postmortem brain tissue obtained from normal subjects and patients dying with Parkinson's disease who were receiving treatment with dopaminergic drugs. Dopamine D1-3 receptors, tyrosine hydroxylase and dopamine transporter mRNA was detected in the uvula and nodulus (lobules 9 and 10, respectively) of the vermis of cerebellum from normal individuals. In Parkinson's disease, the level of dopamine D1 and D3 receptor mRNA was significantly reduced in lobule 9 and the level of tyrosine hydroxylase mRNA was significantly reduced in lobule 10. No alteration in the level of dopamine D2 receptor or dopamine transporter mRNA was found in either lobule in patients with Parkinson's disease. These results show that mRNA expression for the functional components of dopaminergic neurotransmission is present in human cerebellum. The discrete changes in the levels of dopamine D1 and D3 receptors and tyrosine hydroxylase mRNA in cerebellum from l-DOPA treated Parkinson's disease patients suggests that this brain area has a role in the symptoms of Parkinson's disease and/or the beneficial/side-effects of treatment.
Hurley
Michael J
MJ
Neurology Department, University of Miami School of Medicine, Miami, FL, 33136, USA. mhurley@ich.ucl.ac.uk
Mash
Deborah C
DC
Jenner
Peter
P
D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002531:Cerebellum / Q000378:metabolism*; D015259:Dopamine Agents / Q000009:adverse effects / Q000627:therapeutic use; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010300:Parkinson Disease / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D000978:Antiparkinson Agents; D015415:Biomarkers; C493593:DRD3 protein, human; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase