Striatal dopaminergic afferents concentrate in GDNF-positive patches during development and in developing intrastriatal striatal grafts

Glial cell line-derived neurotrophic factor (GDNF) has potent trophic actio n on fetal dopaminergic neurons. We have used a double immunocytochemical a pproach with antibodies that recognize GDNF and tyroxine hydroxylase (TH) o r the phosphoprotein DARPP-32, to study the developmental pattern of their interactions in the rat striatum and in intrastriatal striatal transplants. Postnatally, at one day and also at 1 week, GDNF showed a patchy distribut ion in the striatum, together with a high level of expression in the latera l striatal border, similar to that observed for the striatal marker DARPP-3 2 and also for TH. In the adult striatum, there was diffuse, weak immunopos itivity for GDNF, together with widespread expression of DARPP-32-positive neurons and TH-immunoreactive (TH-ir) fibers. In 1-week-old intrastriatal s triatal transplants, there were some GDNF immunopositive patches within the grafts and although there was not an abundance of TH-positive fibers, the ones that were seen were located in GDNF-positive areas. This was clearly e vident in 2-week-old transplants, where TH-ir fibers appeared selectively c oncentrated in GDNF-positive patches. This pattern was repeated in 3-week-o ld grafts. In co-transplants of mesencephalic and striatal fetal tissue (in a proportion of 1:4), TH-ir somata were located mainly at the borders of a reas that were more strongly immunostained for GDNF, and TH-ir fibers were also abundant in these areas and were found in smaller numbers in regions t hat were weakly positive for GDNF. These results demonstrate that GDNF-ir is coincident with that for TH and D ARPP-32, and suggest that GDNF release by fetal striatal neurons both in no rmal development and in developing striatal grafts may have not only a trop hic but also a tropic influence on TH-ir fibers and may be one of the facto rs that regulate dopaminergic innervation of the striatum. J. Comp. Neurol. 406:199-206, 1999. (C) 1999 Wiley-Liss, Inc.