UP-REGULATION OF STRIATAL D2 RECEPTORS IN THE MPTP-TREATED VERVET MONKEY IS REVERSED BY GRAFTS OF FETAL VENTRAL MESENCEPHALON - AN AUTORADIOGRAPHIC STUDY

Citation
Jd. Elsworth et al., UP-REGULATION OF STRIATAL D2 RECEPTORS IN THE MPTP-TREATED VERVET MONKEY IS REVERSED BY GRAFTS OF FETAL VENTRAL MESENCEPHALON - AN AUTORADIOGRAPHIC STUDY, Brain research, 795(1-2), 1998, pp. 55-62
Citations number
66
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
00068993
Volume
795
Issue
1-2
Year of publication
1998
Pages
55 - 62
Database
ISI
SICI code
0006-8993(1998)795:1-2<55:UOSDRI>2.0.ZU;2-3
Abstract
Although neural transplantation holds promise as a treatment for Parki nson's disease, parkinsonian primates have generally exhibited inconsi stent and incomplete recovery of motor functions following intrastriat al 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 a ctivation. This issue was examined by measuring the effect of transpla nting fetal ventral mesencephalon to the striatum of methyl-4-phenyl-1 ,2,3,6-tetrahydropyridine-treated (MPTP) monkeys on striatal D2 recept or binding. One year after receiving MPTP, D2 receptor binding was upr egulated 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 concentrati on in dorsal striatum of grafted MPTP-treated monkeys was significantl y,higher than in that region of MPTP-treated non-grafted monkeys. In a ddition, dopamine concentration was significantly higher in dorsal com pared to ventral striatum of grafted MPTP-treated monkeys. These data, in addition to those from a previous autoradiographic study on dopami ne uptake site density in these monkeys, strongly supports the hypothe sis that ectopically placed ventral mesencephalon not only produces, b ut maintains the release of sufficient levels of dopamine to restore p ostsynaptic dopamine transmission in regions influenced by graft-deriv ed dopamine. (C) 1998 Elsevier Science B.V. All rights reserved.