Expression of dopamine transporter mRNA and its binding site in fetal nigral cells transplanted into the striatum of 6-OHDA lesioned rat.
Neurological disorders in rat model of hemi-Parkinson's disease can be compensated by the transplantation of fetal nigral cells. However, the role of the dopamine transporter (DAT) in this recovery has not been clarified. To clarify this mechanism, we examined the expression of DAT in the caudate putamen (CPu) by in situ hybridization histochemistry (mRNA) and autoradiography (using the ligand [125I] beta-CIT, which labels DAT) and compared them with the recovery of motor disturbance revealed with methamphetamine-induced rotation. Models were made with the stereotaxic injection of 6-hydroxydopamine into the left side of the substantia nigra pars compacta. Cell suspensions from rat fetus (embryonic day 14-15) were transplanted into the lesioned side of CPu. Methamphetamine-induced rotation, expression of DAT mRNA, and [125I] beta-CIT binding were evaluated 2, 4 and 12 weeks after the transplantation. Methamphetamine-induced rotation recovered partly in the 2nd week and significantly in the 4th week. [125I] beta-CIT binding increased with time and the dense binding was detected 4 and 12 weeks after the transplantation. In all transplanted rats, cells expressing DAT mRNA were found in CPu. These results indicated that transplanted fetal dopaminergic cells maturated in CPu of host animals and extended nerve terminals where high density of DAT binding sites were found.
Fujita
M
M
Division of Tracer Kinetics, Osaka University Medical School, Japan. fujita@orpheus.med.yale.edu
Nishino
H
H
Kumazaki
M
M
Shimada
S
S
Tohyama
M
M
Nishimura
T
T
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000502:physiology; D001667:Binding, Competitive; D016380:Brain Tissue Transplantation; D002352:Carrier Proteins / Q000378:metabolism*; D017690:Cell Transplantation; D003342:Corpus Striatum / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493216:Slc6a3 protein, rat; D016627:Oxidopamine