Partial reversal of increased preproenkephalin messenger ribonucleic acid (mRNA) and decreased preprotachykinin mRNA by foetal dopamine cells in unilateral 6-hydroxydopamine-lesioned rat striatum parallels functional recovery

Abstract

In situ hybridization histochemistry was used to investigate the expression of striatal preproenkephalin and preprotachykinin messenger ribonucleic acid (mRNA) in rats with 6-hydroxydopamine lesions of the nigrostriatal pathway followed 4 weeks later by implantation of foetal dopamine cells into the denervated striatum. Striatal dopamine deafferentation caused an (+)-amphetamine-induced rotational asymmetry, an increase in striatal preproenkephalin mRNA message, and a decrease in striatal preprotachykinin mRNA message relative to control animals. Two months after grafting a foetal ventral mesencephalon suspension, there was reversal of the rotational asymmetry to (+)-amphetamine. At this time the increase in striatal preproenkephalin mRNA was significantly attenuated and the decrease in preprotachykinin mRNA was partially reversed compared to animals with a 6-hydroxydopamine lesion alone. Subregional analysis showed the attenuation of the increase in preproenkephalin mRNA to occur in dorsolateral, dorsomedial and ventromedial, but not ventrolateral, striatal subdivisions. The partial reversal of the decreased preprotachykinin mRNA density after grafting was only statistically significant in the DM and VM subdivisions. These results demonstrate graft-induced partial recovery of striatal function, as judged by preproenkephalin and preprotachykinin mRNA levels, within 2 months of transplantation.