Cellular distribution of the NMDA receptor subunit NMDAR1 in fetal ventral mesencephalon transplants in the dopamine-depleted striatum of a rat.

Abstract

Immunohistochemistry was performed to demonstrate the cellular distribution of N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 in the intrastriatal grafts of a rat model of Parkinson's disease. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal pathway were produced in young adult female rats. Neural transplantation was performed with fetal ventral mesencephalon (VM) tissue (at embryonic day 15) 3 weeks after the 6-OHDA lesions. In the fetal VM in which the tyrosine hydroxylase (TH) immunoreactivity was intensely observed, no NMDAR1 subunit immunoreactivity was detected. Immunopositive cells of NMDAR1 were densely distributed in the intact SNc contralateral to the lesions, in which intense immunoreactivity for TH was observed. In contrast, the cells positive for NMDAR1 in the SNr were scattered. The immunoreactivity for NMDAR1 was markedly decreased in the SNc, but not in the SNr on the lesioned side. Double immunostaining revealed that most TH-positive cells in the SNc showed moderate NMDAR1 immunoreactivity. Within the intrastriatal fetal VM grafts containing TH-positive cells, NMDAR1-positive cells tended to locate homogeneously within the grafts. These were composed of various cell sizes and shapes, but they were mainly medium-sized and aspiny cells. Double immunostaining revealed that a part of the TH-positive cells in the grafts was also immunopositive for NMDAR1. Taken together with our previous studies, it is suggested that both dopaminergic neurons and nondopaminergic neurons in the VM transplants appear to be modified functionally by glutamatergic afferents via various glutamate receptors, including NMDAR1.