Comparison between the decrease of dopamine transporter and that of L-DOPA uptake for detection of early to advanced stage of Parkinson's disease in animal models.
Early diagnosis of Parkinson's disease (PD) is important for the potential application of neuroprotective therapies. The purpose of this study was to assess the detection of the early changes of PD by either imaging the dopamine transporter (DAT) or uptake of L-3,4-dihydroxyphenylalanine (L-DOPA). An early to advanced stage model of PD was induced in rats by stereotaxic injection of 1-10 microg 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta. Using adjacent sections of the same animals, the binding of [I-125]beta-CIT, which labels DAT and the uptake of [C-14]L-DOPA, were evaluated 4 weeks after induction of the lesion. Any decrease in dopaminergic neurons was evaluated by in situ hybridization histochemistry (ISH) by detection of DAT mRNA-positive neurons. In addition, the expression levels of DAT, dopa decarboxylase (DDC), and vesicular monoamine transporter (VMAT2) in each neuron were studied with ISH. Our results show a decrease in both [I-125]beta-CIT binding and [C-14]L-DOPA uptake in parallel with a decrease in DA neurons from early to advanced stage models of PD. The decrease in [C-14]L-DOPA uptake was smaller than that in [I-125]beta-CIT binding in the same animal (P < 0.0001). Expression levels of DAT, DDC, and VMAT2 mRNAs were also decreased with the progression of the disease. Although ISH failed to detect the origin of the discrepancy between [I-125]beta-CIT and [C-14]L-DOPA levels, it was concluded that [C-14]L-DOPA levels underestimated the decrease of dopaminergic neurons and that [I-125]beta-CIT levels more precisely reflected the decrease.
Ito
Y
Y
Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Japan.
Fujita
M
M
Shimada
S
S
Watanabe
Y
Y
Okada
T
T
Kusuoka
H
H
Tohyama
M
M
Nishimura
T
T
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004296:Dopa Decarboxylase / Q000235:genetics / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007980:Levodopa / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010302:Parkinson Disease, Secondary / Q000175:diagnosis* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; 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; C493454:Slc18a2 protein, rat; C493216:Slc6a3 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D007980:Levodopa; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D004296:Dopa Decarboxylase; D003042:Cocaine