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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/299817
- author
- Maciel, EN
; Schierle, Gabriele
LU
; Hansson, Oskar
LU
; Brundin, Patrik
LU
and Castilho, RF
- organization
- publishing date
- 2003
- 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
- Elsevier
- 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
- 2016-04-01 12:19:11
- date last changed
- 2022-01-27 01:56:16
@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}},
keywords = {{NMDA; quinolinic acid; striatum; mitochondrial permeability transition; cyclosporin A; Bcl-2; calcium}},
language = {{eng}},
number = {{2}},
pages = {{430--437}},
publisher = {{Elsevier}},
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}},
doi = {{10.1016/S0014-4886(03)00165-1}},
volume = {{183}},
year = {{2003}},
}