Differential expression of neurotrophin and neurotrophin receptor mRNAs inand adjacent to fetal midbrain grafts implanted into the dopamine-denervated striatum

This study examined the expression of neurotrophins and neurotrophin recept ors in the lesion/transplanted striatum at four different time points after transplantation. The ventral mesencephalic region was dissected from a sin gle rat fetus at embryonic day 14 (E14) and implanted into the denervated s triatum of rats with unilateral 6-hydroxydopamine lesions. Transplanted rat s were killed at 1, 2, 3, or 4 weeks after transplantation surgery and the brains subsequently prepared for semiquantitative in situ hybridization ana lysis of neurotrophin and neurotrophin trk receptors. Hybridization of cRNA probes for trkB or trkC showed a time-dependent reduction within the trans plant during the first 4 weeks after transplantation; hybridization of brai n-derived neurotrophic factor or tyrosine hydroxylase mRNA probes within th e transplant did not change significantly during the same posttransplantati on period. Hybridization of the trkB mRNA probe in host striatum adjacent t o the transplant was significantly higher than probe hybridization in the c orresponding region of the intact striatum during the first 2 weeks after t ransplantation, but by the 3rd and 4th week, probe hybridization in the den ervated/transplanted and intact striatum were the same. Lesioned animals wi thout transplants maintained higher trkB mRNA probe hybridization in the de nervated striatum than in the intact striatum at the same postlesion time p oints suggesting that lesioned/transplanted animals show a normalization of trkB mRNA probe hybridization. Hybridization of the trkC mRNA probe in the lesioned/transplanted striatum was significantly lower than that observed in the intact striatum 4 weeks after transplantation; however, at this same time point we observed a similar reduction of trhC probed hybridization in lesioned animals without transplants. The results of the study show dynami c neurotrophic activity occurring within the transplant and host tissue dur ing the first month of transplant development. (C) 2000 Wiley-Liss, Inc.