Early and widespread normalization of dopamine-neuropeptide Y interactions in the rat striatum after transplantation of fetal mesencephalon cells.

Graft-to-host interactions were examined at cellular level, by measuring changes in the immunoreactivity of striatal interneurons expressing neuropeptide Y after dopamine denervation and transplantation of fetal mesencephalon neurons into the striatum of adult rats. Mesencephalic cell suspensions were implanted unilaterally into the dorsal part of the striatum in rats two weeks after intranigral injection of 6-hydroxydopamine. One month and three to four months later, rats showing abolition of amphetamine-induced turning were perfused. Serial brain sections containing intrastriatal grafts were treated for tyrosine hydroxylase and neuropeptide Y immunocytochemistry, and neuropeptide Y-immunoreactive neurons were quantified in various parts of the striatal surface and compared with the striatum of controls and age-matched rats with lesions. Biochemical analyses of dopamine and dihydroxyphenyl acetic acid tissue levels and [3H]dopamine uptake were also performed on striatal samples from similar groups of normal, lesioned and transplanted rats. As early as one month post-grafting, a complete reversal of the increase in the number of neuropeptide Y-immunoreactive neurons occurring after 6-hydroxydopamine lesion was observed in dopamine-grafted animals, although a partial restoration of the tyrosine hydroxylase immunostaining and a recovery of 8% dopamine tissue level were observed in the striata of grafted as compared to normal rats. This effect on the host immunoreactivity was found to be specific to dopamine grafts, since no reversal was observed in sham-spinal cord-transplanted rats. Moreover, similar degrees of normalization were recorded either in the total striatum, or in the area immediately adjacent to the graft, or even in the zone most sensitive to dopamine denervation in terms of neuropeptide Y immunoreactivity. No more pronounced functional effects were observed three to four months after transplantation. These data suggest that grafted dopamine neurons are able to induce rapid and extensive host responsiveness, possibly by means of mechanisms involving synaptic and diffuse release of dopamine and adaptive changes in the host brain. These data may provide a cellular basis for interpreting larger behavioural recoveries than those expected to occur with dopamine grafts in view of the partial restoration of the dopaminergic innervation.