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FK506 and cyclosporin A enhance the survival of cultured and grafted rat embryonic dopamine neurons

In English

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.

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