Recovery after nigral grafting in 6-hydroxydopamine lesioned rats is due to graft function and not significantly influenced by the remaining ipsilateral or contralateral host dopaminergic system

The aim of this study was to evaluate whether the recovery observed after g rafting of fetal nigral cells in 6-hydroxydopamine lesioned rats is due to the graft itself, and whether the participation of the remaining host dopam inergic system is necessary. The effects of unilateral B-hydroxydopamine le sion on rotational behavior were not significantly affected by sham graftin g or by sham grafting plus repent ipsilateral lesion, but were suppressed b y nigral grafting, and by contralateral lesion. Immunohistochemical and in situ hybridization study of right striata of rats subjected to right-side l esion then right-side sham-grafting, and of right and left striata from rat s subjected to right-side lesion then right-side sham-grafting then repeat right-side lesion then left-side lesion, revealed (a) no significant amphet amine-induced Fos activation (b) marked increases in preproenkephalin mRNA levels, and (c) decreases in preprotachykinin levels, with no significant d ifferences in any of these variables among these three types of striata. Af ter nigral grafting, however, intense Fos expression was observed in the st riatum, and preproenkephalin and preproenkephalin mRNA levels returned to n ormal. This recovery was maintained after subsequent repeat ipsilateral 6-h ydroxydopamine lesion followed by contralateral lesion. The results demonst rate that, after dopaminergic denervation, the nigral graft itself is able to induce recovery in the assessed parameters, and that these effects of gr afting into striata with maximal unilateral 6-hydroxydopamine lesion are du e to graft function, and are not significantly influenced by the remaining ipsilateral or contralateral host dopaminergic system. Additionally, it is interesting to note that bilateral denervation led to changes in striatal p reproenkephalin and preproenkephalin mRNA levels similar to those observed after unilateral lesion. (C) 1999 Elsevier Science B.V. All rights reserved .