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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 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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author
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
ISSN
0014-4886
DOI
10.1006/exnr.2000.7405
language
English
LU publication?
yes
id
a8da9ee7-abc5-4ae6-a843-067be1aef567 (old id 1117114)
date added to LUP
2008-07-02 16:34:48
date last changed
2017-01-01 04:58:37
@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},
  keyword      = {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},
  volume       = {164},
  year         = {2000},
}