LOCALIZATION OF DOPAMINE-RECEPTORS AND ASSOCIATED MESSENGER-RNA IN TRANSPLANTS OF HUMAN FETAL STRIATAL TISSUE IN RODENTS WITH EXPERIMENTAL HUNTINGTONS-DISEASE

Huntington's Disease (HD) is characterized by deficits in motor and co gnitive functions. This neurodegenerative disease shows an extensive l oss of medium-sized spiny projection neurons (GABAergic) within the ne ostriatum. With the loss of these neurons, there is a concomitant loss of associated receptors, such as those for GABA, glutamate, and dopam ine. In the present study, we have addressed the question of whether d opamine receptors are se-established in the lesioned rodent striatum f ollowing the transplantation of human striatal cells. Human striatal c ell suspension or saline (transplant controls) was injected into the s triatum of rats previously lesioned with quinolinic acid (QA). Three-n ine months following transplantation, the animals were sacrificed and the brains were processed for receptor autoradiography and in situ hyb ridization of dopamine D1 and D2 receptor subtypes. Our results demons trate that animals transplanted with human striatal cells show a signi ficant increase in D1 receptors following transplantation when compare d to the lesion area in control animals, while D1 receptor mRNA remain s unchanged. In contrast to D1 receptor binding, D2 receptor levels ar e not increased in the lesioned and transplanted area of the striatum when compared to controls; however, D2 receptor mRNA levels are signif icantly increased. These results demonstrate that at the times the ani mals were examined, D1 and D2 receptors were differentially regulated. Our results further indicate that human striatal primordium will surv ive following transplantation and will express D1 receptors and D2 rec eptor 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. (C) 1997 Elsevier Science Ire land Ltd.