FK506 and cyclosporin A enhance the survival of cultured and grafted rat embryonic dopamine neurons.
We examined the effects of the immunophilin ligands and calcineurin inhibitors FK506 and cyclosporin A on the survival of rat embryonic dopamine (tyrosine hydroxylase (TH)-immunoreactive) neurons. The protective effects of FK506 and cyclosporin A were first studied in dissociated mesencephalic cell cultures subjected to serum deprivation. Significant increases in both the total number of surviving mesencephalic cells and the number of surviving TH-immunoreactive neurons were observed when FK506 or cyclosporin A was present following withdrawal of serum from the culture medium. In a second series of experiments, FK506 increased the survival of dopamine neurons when added only to a hibernation medium in which donor tissue pieces were stored for 7 days prior to preparation of the cultures. In a third set of experiments, we investigated the effects of FK506 and cyclosporin A on the survival of grafted rat embryonic dopamine neurons. When FK506 or cyclosporin A was present during tissue preparation and in the final mesencephalic cell suspension used for grafting, the survival of TH-immunoreactive neurons implanted in the striatum increased to around 185% of control values. In contrast, treatment of graft recipient rats, but not the graft suspension itself, with immunosuppressive doses of FK506 or cyclosporin A did not augment the survival of grafted TH-immunoreactive neurons. We conclude that administration of FK506 during storage of embryonic mesencephalic tissue and FK506 or cyclosporin A during preparation of nigral cell suspensions used for grafting can increase the survival of grafted embryonic dopamine neurons.
Castilho
R F
RF
Section for Neuronal Survival, Wallenberg Neuroscience Center, Lund, Sweden.
Hansson
O
O
Brundin
P
P
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006085:Graft Survival / Q000187:drug effects; D008636:Mesencephalon / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism* / Q000637:transplantation; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*; D014021:Tissue Preservation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016895:Culture Media, Serum-Free; D016572:Cyclosporine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D016559:Tacrolimus