Intrastriatal implants of fetal mesencephalic cells attenuate the increases in striatal proenkephalin mRNA observed after unilateral 6-hydroxydopamine-induced lesions of the striatum

Abstract

Unilateral injections of 6-hydroxydopamine (6-OHDA) cause significant bilateral increases in striatal proenkephalin (PEK) mRNA in rat brain. We have tested the possibility that implantation of fetal mesencephalic cells can normalize these changes. Two types of grafts were used: 1. 1) embryonic day-15 mesencephalic cells 2. 2) embryonic day-15 cells which have been modified with a retroviral vector containing a cDNA for protein kinase C (PKC). At two months after grafting, both cell types cause significant attenuation of the increases which occurred on the side of the lesion. However, only the PKC-modified cells cause normalization of the changes on the contralateral side. These observations indicate that, in addition to normalizing supersensitive striatal dopamine (DA) D2 receptors, embryonic cells can also attenuate the alterations in PEK mRNA observed after lesions of the nigrostriatal DA system. The finding that the PKC-modified cells caused bilateral effects in the striatum suggests that second messenger systems may play a role in the bilateral improvement reported in parkinsonian patients who had gotten unilateral intrastriatal transplants.