Co-grafts of fetal ventral mesencephalon and fibroblasts expressing sonic hedgehog: effect on survival and function of dopamine grafts.
Fibroblasts derived from the Rat2 parental cell line were genetically modified to express the cell-associated form of Sonic hedgehog (Shh) and then co-grafted along with E14 fetal ventral mesencephalon (VM) tissue into the denervated striatum of F344 rats; fetal VM grafts alone or co-grafts using the nonexpressing Rat2 fibroblasts served as controls. Seven weeks after grafting, co-grafts of fetal VM and fibroblasts expressing Shh (Rat2/Shh) contained significantly more tyrosine hydroxylase-positive (TH+) neurons than either the fetal VM grafts or co-grafts of fetal VM plus nonexpressing fibroblasts (Rat2). Despite a significantly higher yield of grafted TH+ neurons in the fetal VM + Rat2/Shh co-grafts than in either of the other two control groups, amphetamine-induced rotational behavior scores were not significantly different between any of the three treatment groups. The number of TH+ neurons in the Rat2 (nonexpressing) co-grafts was significantly lower than the other two treatment groups. The results from this study suggest that fibroblasts expressing Shh may improve the number of co-grafted dopamine neurons, but do not improve the functional capacity of the graft in terms of improving amphetamine-induced rotational behavior.
Yurek
D M
DM
Department of Surgery/Neurosurgery, University of Kentucky College of Medicine, Lexington 40536-0305, USA. dyure00@pop.uky.edu
Fletcher-Turner
A
A
Moore
J
J
Chai
L
L
Mahanthappa
N
N
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016380:Brain Tissue Transplantation; D002452:Cell Count; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D016332:Fetal Tissue Transplantation; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation*; D015870:Gene Expression / Q000187:drug effects; D006085:Graft Survival; D053823:Hedgehog Proteins; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000502:physiology / Q000637:transplantation*; D009474:Neurons / Q000737:chemistry / Q000502:physiology / Q000637:transplantation; D051381:Rats; D011916:Rats, Inbred F344; D012399:Rotation; D015534:Trans-Activators / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D053823:Hedgehog Proteins; D015534:Trans-Activators; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine