FK506 and cyclosporin A enhance the survival of cultured and grafted rat embryonic dopamine neurons
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2000
Språk
Engelska
Sidor
94-101
Publikation/Tidskrift/Serie
Experimental Neurology
Volym
164
Issue
1
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Neurology
Nyckelord
- cell death
- cyclosporin A
- dopamine
- FK506
- immunophilin ligand
- intracerebral transplantation
- Parkinson's disease
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0014-4886