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.

• Författare: EN Maciel; Gabriele Schierle; Oskar Hansson; Patrik Brundin; RF Castilho
• Avdelning/ar: Institutionen för experimentell medicinsk vetenskap; Klinisk minnesforskning
• Publiceringsår: 2003
• Språk: Engelska
• Sidor: 430-437
• Publikation/Tidskrift/Serie: Experimental Neurology
• Volym: 183
• Issue: 2
• Länkar: http://dx.doi.org/10.1016/S0014-4886(03)00165-1
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Neurology
• Nyckelord: NMDA; quinolinic acid; striatum; mitochondrial permeability transition; cyclosporin A; Bcl-2; calcium
• Status: Published
• Forskningsgrupp: Clinical Memory Research
• ISBN/ISSN/Övrigt: ISSN: 0014-4886