Dopamine transporter (Dat) and synaptic vesicle amine transporter (VMAT2) gene expression in the substantia nigra of control and Parkinson's disease.
The cellular expression of DAT mRNA and VMAT2 mRNA was investigated in sections of the human post-mortem substantia nigra in control and Parkinson's disease tissue using in situ hybridisation techniques. Short synthetic oligodeoxynucleotides were used to detect these gene transcripts at the cellular level. In the control human nigra, high levels of expression were seen in all sub-divisions of the substantia nigra, especially within medial regions. By contrast, the level of expression of both DAT mRNA and VMAT2 mRNA was markedly reduced in Parkinson's disease; these reductions in hybridisation signal were associated with (i) a marked loss of dopamine-containing cells in the substantia nigra, and (ii) a reduction in both DAT and VMAT2 signal per cell in the remaining pigmented neurones. These disease-related decreases in the cellular abundance of both DAT and VMAT2 gene transcripts in the surviving cells of the parkinsonian nigra may reflect compensatory changes in catecholamine signalling or may be a consequence of neuronal dysfunction.
Harrington
K A
KA
Department of Neurobiology, Babraham Institute, Cambridge, UK.
Augood
S J
SJ
Kingsbury
A E
AE
Foster
O J
OJ
Emson
P C
PC
D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002452:Cell Count; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009479:Neuropeptides; D010300:Parkinson Disease / Q000378:metabolism*; D012016:Reference Values; D013378:Substantia Nigra / Q000378:metabolism*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C493452:SLC18A2 protein, human; C493214:SLC6A3 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D004298:Dopamine