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