53 189

Cited 0 times in

Cyclosporine induces neuronal apoptosis and selective oligodendrocyte death in cortical cultures.

Authors
McDonald, JW; Goldberg, MP; Gwag, BJ; Chi, SI; Choi, DW
Citation
Annals of neurology, 40(5):750-758, 1996
Journal Title
Annals of neurology
ISSN
0364-51341531-8249
Abstract
Cyclosporine is used clinically as an immunosuppressant, but carries a risk of central nervous system toxicity due to undefined mechanisms. We examined the ability of cyclosporine exposure to kill cultured mouse cortical neurons and glia. Mixed neuron/glial cultures exposed to 1 to 20 microM cyclosporine for 24 to 48 hours developed concentration-dependent neuronal death, with most neurons destroyed by 20 microM cyclosporine. This neuronal death was characterized by cell body shrinkage and blebbing, chromatin condensation, and internucleosomal DNA fragmentation, consistent with apoptosis. Neuronal death was reduced by addition of cycloheximide, brain-derived neurotrophic factor, or insulin-like growth factor I but not N-methyl-D-aspartate- or AMPA-type glutamate receptor antagonists. Oligodendrocytes were more sensitive to cyclosporine-induced damage than were neurons, but astrocytes were relatively resistant. Oligodendrocyte death was accompanied by positive TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling) staining and was attenuated by application of ciliary neurotrophic factor or insulin-like growth factor I but not glutamate receptor antagonists. Present observations raise the possibility that the central nervous system toxicity syndrome associated with cyclosporine may be caused by the drug-induced death of oligodendrocytes and neurons.
MeSH terms
AnimalsApoptosis/*drug effectsBrain-Derived Neurotrophic Factor/pharmacologyCell Death/*drug effectsCells, CulturedCerebral Cortex/*cytologyChromatin/drug effectsCiliary Neurotrophic FactorCoculture TechniquesCyclosporine/antagonists & inhibitors/*toxicityDNA/analysisDNA Nucleotidylexotransferase/metabolismDizocilpine Maleate/pharmacologyExcitatory Amino Acid Antagonists/pharmacologyFetusImmunosuppressive Agents/toxicityInsulin-Like Growth Factor I/pharmacologyMiceNerve Growth Factors/pharmacologyNerve Tissue Proteins/pharmacologyNeurons/cytology/*drug effectsNeurotoxins/*toxicityOligodendroglia/cytology/*drug effects/pathologyReceptors, N-Methyl-D-Aspartate/antagonists & inhibitors
DOI
10.1002/ana.410400511
PMID
8957016
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
Files in This Item:
Full-Text Not Available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse