Upregulation of striatal D2 receptors in the MPTP-treated vervet monkey is reversed by grafts of fetal ventral mesencephalon: an autoradiographic study.
Although neural transplantation holds promise as a treatment for Parkinson's disease, parkinsonian primates have generally exhibited inconsistent and incomplete recovery of motor functions following intrastriatal grafting of fetal ventral mesencephalon. One possible contributing factor to this variable response is lack of appropriate integration of donor neurons with host striatal circuitry with the result that there is insufficient dopamine release and postsynaptic dopamine receptor activation. This issue was examined by measuring the effect of transplanting fetal ventral mesencephalon to the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP) monkeys on striatal D2 receptor binding. One year after receiving MPTP, D2 receptor binding was upregulated in the dorsal and ventral striatum of African green monkeys. Grafting of fetal ventral mesencephalon to the dorsal striatum of MPTP-treated monkeys 9 months before sacrifice, eliminated the D2 receptor upregulation in dorsal, but not ventral, region. Dopamine concentration in dorsal striatum of grafted MPTP-treated monkeys was significantly higher than in that region of MPTP-treated non-grafted monkeys. In addition, dopamine concentration was significantly higher in dorsal compared to ventral striatum of grafted MPTP-treated monkeys. These data, in addition to those from a previous autoradiographic study on dopamine uptake site density in these monkeys, strongly supports the hypothesis that ectopically placed ventral mesencephalon not only produces, but maintains the release of sufficient levels of dopamine to restore postsynaptic dopamine transmission in regions influenced by graft-derived dopamine.
Elsworth
J D
JD
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA. jd.elsworth.yale@axion.org
Brittan
M S
MS
Taylor
J R
JR
Sladek
J R
JR
Redmond
D E
DE
Innis
R B
RB
Zea-Ponce
Y
Y
Roth
R H
RH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001572:Benzofurans; D016380:Brain Tissue Transplantation; D002522:Chlorocebus aethiops; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000601:surgery; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology*; D016332:Fetal Tissue Transplantation; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008636:Mesencephalon / Q000637:transplantation*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism / Q000601:surgery; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D001572:Benzofurans; D015259:Dopamine Agents; D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine