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

Summary, in English

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: EN Maciel; Gabriele Schierle; Oskar Hansson; Patrik Brundin; RF Castilho
• Department/s: Department of Experimental Medical Science; Clinical Memory Research
• Publishing year: 2003
• Language: English
• Pages: 430-437
• Publication/Series: Experimental Neurology
• Volume: 183
• Issue: 2
• Links: http://dx.doi.org/10.1016/S0014-4886(03)00165-1
• Document type: Journal article
• Publisher: Elsevier
• Topic: Neurology
• Keywords: NMDA; quinolinic acid; striatum; mitochondrial permeability transition; cyclosporin A; Bcl-2; calcium
• Status: Published
• Research group: Clinical Memory Research
• ISBN/ISSN/Other: ISSN: 0014-4886