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 inhibit ors FK506 and cyclosporin A on the survival of rat embryonic dopamine (tyro sine hydroxylase (TH)-immmunoreactive) neurons. The protective effects of F K506 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 pre sent following withdrawal of serum from the culture medium. In a second ser ies of experiments, FK506 increased the survival of dopamine neurons when a dded 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 experime nts, we investigated the effects of FK506 and cyclosporin A on the survival of grafted rat embryonic dopamine neurons, When FH506 or cyclosporin A was present during tissue preparation and in the final mesencephalic cell susp ension used for grafting, the survival of TH-immunoreactive neurons implant ed in the striatum increased to around 185% of control values, In contrast, treatment of graft recipient rats, but not the graft suspension itself, wi th immunosuppressive doses of FK506 or cyclosporin A did not augment the su rvival of grafted TH-immunoreactive neurons. We conclude that administratio n of FK506 during storage of embryonic mesencephalic tissue and FK506 or cy closporin A during preparation of nigral cell suspensions used for grafting can increase the survival of grafted embryonic dopamine neurons. (C) 2000 Academic Press.