Fetal intra-nigral ventral mesencephalon and kidney tissue bridge transplantation restores the nigrostriatal dopamine pathway in hemi-parkinsonian rats

We have previously demonstrated that intranigral transplantation of fetal v entral mesencephalic (VM) tissue and nigrostriatal administration of glial cell line-derived neurotrophic factor (GDNF) restores striatal dopamine inp ut in hemiparkinsonian rats, Since it has been found that GDNF is highly ex pressed in fetal kidney, we examined the possibility that fetal kidney tiss ue may provide trophic support, similar to GDNF, to an intranigral dopamine (DA) transplant and restore the nigrostriatal pathway. Adult Sprague-Dawle y rats were anesthetized and unilaterally injected with 6-hydroxydopamine ( 6-OHDA) into the medial forebrain bundle. Completeness of the lesion was ev aluated by measuring amphetamine-induced rotation. One month after 6-OHDA l esioning, fetal VM cells were grafted into the lesioned nigral area followe d by transplantation of fetal kidney tissue or vehicle along a pathway from nigra to striatum. Animals receiving these transplants showed a significan t decrease both in amphetamine-induced rotation and in postural asymmetry 1 to 3 months after grafting. Immunocytochemical studies demonstrated tyrosi ne hydroxylase (TH) positive fiber tracts in the lesioned striatum. Control animals that received vehicle injection after the intranigral graft or no transplantation showed no alterations in amphetamine-induced turning and no TH-positive fibers in the lesioned striatum. These results indicate that c ombinations of fetal nigral and kidney transplants may restore the nigrostr iatal DA pathway in Parkinsonian rats. As fetal kidney contains a variety o f trophic proteins, it may provide a synergistic admixture to optimally pro mote DA fiber outgrowth. (C) 2001 Elsevier Science B.V. All rights reserved .