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Cyclosporin A and Bcl-2 do not inhibit quinolinic acid-induced striatal excitotoxicity in rodents

Maciel, EN; Schierle, Gabriele LU ; Hansson, Oskar LU ; Brundin, Patrik LU and Castilho, RF (2003) In Experimental Neurology 183(2). p.430-437
Abstract
Mitochondrial permeability transition (MPT) is a nonselective inner membrane permeabilization that contributes to neuronal cell death under circumstances such as brain trauma, ischemia, and hypoglycemia. Here we study the participation of MPT and the Bcl-2-sensitive apoptotic cell death pathway in glutamate receptor-mediated excitotoxicity. Intrastriatal infusions of the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid caused massive striatal neurodegeneration in both rats and mice. Interestingly, transgenic mice overexpressing human Bcl-2 and rats systemically treated with cyclosporin A did not exhibit reduced sensitivity to quinolinic acid-induced striatal toxicity. Both Bcl-2 and cyclosporin A are inhibitors of MPT; in... (More)
Mitochondrial permeability transition (MPT) is a nonselective inner membrane permeabilization that contributes to neuronal cell death under circumstances such as brain trauma, ischemia, and hypoglycemia. Here we study the participation of MPT and the Bcl-2-sensitive apoptotic cell death pathway in glutamate receptor-mediated excitotoxicity. Intrastriatal infusions of the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid caused massive striatal neurodegeneration in both rats and mice. Interestingly, transgenic mice overexpressing human Bcl-2 and rats systemically treated with cyclosporin A did not exhibit reduced sensitivity to quinolinic acid-induced striatal toxicity. Both Bcl-2 and cyclosporin A are inhibitors of MPT; in addition Bcl-2 also inhibits apoptotic stimuli-mediated release of mitochondrial apoptogenic factors. Isolated brain mitochondria from cyclosporin A-treated rats showed resistance to Ca2+-induced dissipation of the membrane potential, indicating protection against MPT. We conclude that quinolinic acid-mediated striatal excitotoxicity is not dependent on MPT and Bcl-2-sensitive apoptotic cell death pathways. (C) 2003 Elsevier Science (USA). All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
NMDA, quinolinic acid, striatum, mitochondrial permeability transition, cyclosporin A, Bcl-2, calcium
in
Experimental Neurology
volume
183
issue
2
pages
430 - 437
publisher
Academic Press
external identifiers
  • wos:000185724600019
  • pmid:14552883
  • scopus:0141560577
ISSN
0014-4886
DOI
10.1016/S0014-4886(03)00165-1
language
English
LU publication?
yes
id
58b95fb2-6adc-45ea-a7f9-e62b5cd5dd49 (old id 299817)
date added to LUP
2007-09-17 19:03:00
date last changed
2018-10-03 10:50:04
@article{58b95fb2-6adc-45ea-a7f9-e62b5cd5dd49,
  abstract     = {Mitochondrial permeability transition (MPT) is a nonselective inner membrane permeabilization that contributes to neuronal cell death under circumstances such as brain trauma, ischemia, and hypoglycemia. Here we study the participation of MPT and the Bcl-2-sensitive apoptotic cell death pathway in glutamate receptor-mediated excitotoxicity. Intrastriatal infusions of the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid caused massive striatal neurodegeneration in both rats and mice. Interestingly, transgenic mice overexpressing human Bcl-2 and rats systemically treated with cyclosporin A did not exhibit reduced sensitivity to quinolinic acid-induced striatal toxicity. Both Bcl-2 and cyclosporin A are inhibitors of MPT; in addition Bcl-2 also inhibits apoptotic stimuli-mediated release of mitochondrial apoptogenic factors. Isolated brain mitochondria from cyclosporin A-treated rats showed resistance to Ca2+-induced dissipation of the membrane potential, indicating protection against MPT. We conclude that quinolinic acid-mediated striatal excitotoxicity is not dependent on MPT and Bcl-2-sensitive apoptotic cell death pathways. (C) 2003 Elsevier Science (USA). All rights reserved.},
  author       = {Maciel, EN and Schierle, Gabriele and Hansson, Oskar and Brundin, Patrik and Castilho, RF},
  issn         = {0014-4886},
  keyword      = {NMDA,quinolinic acid,striatum,mitochondrial permeability transition,cyclosporin A,Bcl-2,calcium},
  language     = {eng},
  number       = {2},
  pages        = {430--437},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Cyclosporin A and Bcl-2 do not inhibit quinolinic acid-induced striatal excitotoxicity in rodents},
  url          = {http://dx.doi.org/10.1016/S0014-4886(03)00165-1},
  volume       = {183},
  year         = {2003},
}