Evidence for target-specific outgrowth from subpopulations of grafted human dopamine neurons

Clinical and experimental grafting in Parkinson's disease has shown the nee d for enhanced survival of dopamine neurons to obtain improved functional r ecovery. In addition, it has been suggested that a limited number of surviv ing dopamine neurons project to the dopamine-denervated host striatum. The aim of this study was to investigate if subpopulations of ventral mesenceph alic dopamine neurons project to their normal targets, i.e., dorsal vs. ven tral striatum. Following implantation of human ventral mesencepahlic tissue into the lateral ventricle of dopamine-depleted rats, human-derived dopami ne reinnervation was achieved both in dorsal and ventral striatum. Treatmen t with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) r esulted in a degeneration of tyrosine hydroxylase (TH)-immunoreactive nerve fibers in dorsal striatum but not in ventral areas in some animals, while MPTP was without effect in other animals. TH-immunoreactive neurons were sm all and appeared shrunken in animals carrying grafts affected by the MPTP t reatment. In conclusion, grafted dopamine neurons projected nerve fibers in to areas that they normally innervate. Thus, when searching for factors tha t may enhance survival of grafted dopamine neurons it is important to study which subpopulation(s) of ventral mesencephalic dopamine neurons is affect ed, such that a proper reinnervation may be achieved. Microsc. Res. Tech. 5 4:287-297, 2001. (C) 2001 Wiley-Liss, Inc.