Localization of dopamine receptors and associated mRNA in transplants of human fetal striatal tissue in rodents with experimental Huntington's disease.
Huntington's Disease (HD) is characterized by deficits in motor and cognitive functions. This neurodegenerative disease shows an extensive loss of medium-sized spiny projection neurons (GABAergic) within the neostriatum. With the loss of these neurons, there is a concomitant loss of associated receptors, such as those for GABA, glutamate, and dopamine. In the present study, we have addressed the question of whether dopamine receptors are re-established in the lesioned rodent striatum following the transplantation of human striatal cells. Human striatal cell suspension or saline (transplant controls) was injected into the striatum of rats previously lesioned with quinolinic acid (QA). Three nine months following transplantation, the animals were sacrificed and the brains were processed for receptor autoradiography and in situ hybridization of dopamine D1 and D2 receptor subtypes. Our results demonstrate that animals transplanted with human striatal cells show a significant increase in D1 receptors following transplantation when compared to the lesion area in control animals, while D1 receptor mRNA remains unchanged. In contrast to D1 receptor binding, D2 receptor levels are not increased in the lesioned and transplanted area of the striatum when compared to controls; however, D2 receptor mRNA levels are significantly increased. These results demonstrate that at the times the animals were examined, D1 and D2 receptors were differentially regulated. Our results further indicate that human striatal primordium will survive following transplantation and will express D1 receptors and D2 receptor mRNA that are depleted in the QA lesioned rodent striatum. This study compliments and extends previous findings on human striatal cell transplantation in rodent models of HD.
Pundt
L L
LL
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis 55455, USA.
Narang
N
N
Kondoh
T
T
Low
W C
WC
D000818:Animals; D001345:Autoradiography; D016380:Brain Tissue Transplantation / Q000502:physiology*; D017690:Cell Transplantation / Q000502:physiology; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D017072:Neostriatum / Q000637:transplantation*; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000378:metabolism; D013462:Sulfur Radioisotopes
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013462:Sulfur Radioisotopes