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

Castilho, Roger F ; Hansson, Oskar LU orcid and Brundin, Patrik LU (2000) In Experimental Neurology 164(1). p.94-101
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell death, cyclosporin A, dopamine, FK506, immunophilin ligand, intracerebral transplantation, Parkinson's disease
in
Experimental Neurology
volume
164
issue
1
pages
94 - 101
publisher
Academic Press
external identifiers
  • pmid:10877919
  • scopus:0033913626
  • pmid:10877919
ISSN
0014-4886
DOI
10.1006/exnr.2000.7405
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Psychiatry/Primary Care/Public Health (013240500), Neuronal Survival (013212041)
id
a8da9ee7-abc5-4ae6-a843-067be1aef567 (old id 1117114)
date added to LUP
2016-04-01 12:15:04
date last changed
2025-03-13 20:51:15
@article{a8da9ee7-abc5-4ae6-a843-067be1aef567,
  abstract     = {{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.}},
  author       = {{Castilho, Roger F and Hansson, Oskar and Brundin, Patrik}},
  issn         = {{0014-4886}},
  keywords     = {{cell death; cyclosporin A; dopamine; FK506; immunophilin ligand; intracerebral transplantation; Parkinson's disease}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{94--101}},
  publisher    = {{Academic Press}},
  series       = {{Experimental Neurology}},
  title        = {{FK506 and cyclosporin A enhance the survival of cultured and grafted rat embryonic dopamine neurons}},
  url          = {{http://dx.doi.org/10.1006/exnr.2000.7405}},
  doi          = {{10.1006/exnr.2000.7405}},
  volume       = {{164}},
  year         = {{2000}},
}