Intranigral transplantation of solid tissue ventral mesencephalon or striatal grafts induces behavioral recovery in 6-OHDA-lesioned rats

Parkinson's disease (PD) is characterized by a degeneration of the dopamine (DA) pathway from the substantia nigra (SN) to the basal forebrain. Prior studies in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats have primari ly concentrated on the implantation of fetal ventral mesencephalon (VM) int o the striatum in attempts to restore DA function in the target. We implant ed solid blocks of fetal VM or fetal striatal tissue into the SN to investi gate whether intra-nigral grafts would restore motor function in unilateral ly 6-OHDA-lesioned rats. Intra-nigral fetal striatal and VM grafts elicited a significant and long-lasting reduction in apomorphine-induced rotational behavior. Lesioned animals with ectopic grafts or sham surgery as well as animals that received intra-nigral grafts of fetal cerebellar cortex showed no recovery of motor symmetry. Subsequent immunohistochemical studies demo nstrated that VM grafts, but not cerebellar grafted tissue expressed tyrosi ne hydroxylase (TH)-positive cell bodies and were associated with the inner vation by TH-positive fibers into the lesioned SN as well as adjacent brain areas. Striatal grafts were also associated with the expression of TH-posi tive cell bodies and fibers extending into the lesioned SN and an induction of TH-immunolabeling in endogenous SN cell bodies. This finding suggests t hat trophic influences of transplanted fetal striatal tissue can stimulate the re-expression of dopaminergic phenotype in SN neurons following a 6-OHD A lesion. Our data support the hypothesis that a dopaminergic re-innervatio n of the SN and surrounding tissue by a single solid tissue graft is suffic ient to improve motor asymmetry in unilateral 6-OHDA-lesioned rats. (C) 200 1 Elsevier Science B.V. All rights reserved.