Survival and differentiation of fetal ventral mesencephalon cells after transplantation into hemiparkinsonian rat model
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Parkinson's disease (PD) is a degenerative disorder characterized by a loss of substantia nigra dopaminergic neurons with a consequent reduction in the striatal dopamine (DA). Modeling groups (n=10) were divided into 7-day (n=5) and 14-day groups (n=5) postlesion. Rat embryonic day 13.5 (E13.5) ventral mesencephalic cells were primarily cultured. Transplanting groups (n=9) were subdivided into transplantation groups (n=5) and control groups (n=4). In modeling study, behavioral tests of degenerative alterations of 6-hydroxydopamine (6-OHDA) lesioned unilateral nigral dopaminergic neurons showed over 240 contralateral turns per 40 min to the lesion side in response to apomorphine administration in 3 of 7-day and 2 of 14-day groups. One day postlesion, significant rotational behavior was critical for successful PD model. In primary culture, robust growth of the precursor cells from the embryonic ventral mesencephalon (VM) in neurotrophic factor-free medium was viewed between 5 and 7 days postplating. Thereafter, the survival cells gradually decreased and disappeard 2 weeks postseeding. In transplanting experiment, the VM-derived cells could survive and differentiate in the striatum, neocortex and corpus callosum of adjacent grafts. Tyrosine hydroxylase (TH)-positive cells were observed of the majority of grafted on the periphery of the graft area with fewer cells being seen in the center of the graft. The survival rates of graft-derived dopaminergic neurons peaked at 4 weeks after transplantation, thereafter, gradually declined with time. The decrease of rotational behavior associated with intrastriatal VM grafts was not observed in our research. Together, these findings indicate that (1) the extent of drug-induced rotational asymmetry corresponded to the amount of degenerative alterations of 6-OHDA-lesioned unilateral nigral dopaminergic neurons, (2) strong growth of the embryonic VM cells in primary culture (neurotrophic factor-free) was shown between 5 and 7 days postseeding, and (3) graft-derived dopaminergic neurons could survive in a percent of 2.32±0.34% to 8.40±1.83% with the peak number at 4 weeks after transplantation.