Cyclosporine induces neuronal apoptosis and selective oligodendrocyte death in cortical cultures

Annals of Neurology
J W McDonaldD W Choi

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 ...Continue Reading

References

Nov 1, 1992·The Journal of Cell Biology·Y GavrieliS A Ben-Sasson
Jun 15, 1992·FEBS Letters·K M BroekemeierD R Pfeiffer
Jan 5, 1991·BMJ : British Medical Journal·A W Thomson, G H Neild
Aug 9, 1990·The New England Journal of Medicine·R L Hughes
Dec 21, 1989·The New England Journal of Medicine·B D Kahan
Aug 1, 1989·Transplantation·L FamiglioR Fisher
Aug 1, 1988·Kidney International·T StrzeleckiM Menon
Mar 24, 1988·The New England Journal of Medicine·D M Mann, M M Esiri
Oct 1, 1987·The New England Journal of Medicine·P C de GroenR A Krom
Jan 12, 1985·British Medical Journal·M BeamanJ Walls
Nov 17, 1984·Lancet·C B ThompsonE D Thomas
Dec 1, 1993·Journal of Molecular and Cellular Cardiology·E J Griffiths, A P Halestrap
Oct 1, 1995·Experimental Neurology·J Y KohD W Choi
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T M DawsonS H Snyder
May 1, 1994·Journal of Neuroscience Research·C A CsernanskyD W Choi
Nov 1, 1994·Annals of Neurology·R A Patchell
Jan 1, 1993·Annual Review of Neuroscience·E M Johnson, T L Deckwerth
Mar 1, 1993·The British Journal of Radiology·L MonteiroJ Rocha

❮ Previous
Next ❯

Citations

Sep 17, 1999·Muscle & Nerve·D D Mikol, E L Feldman
Apr 1, 1997·Annals of Neurology·A J Windebank
Feb 29, 2008·Journal of Anesthesia·Yukiko NodaShosuke Takahashi
Oct 3, 2001·Current Treatment Options in Neurology·Rifaat M. Bashir
Sep 3, 2003·Biochemical and Biophysical Research Communications·Jung-Ae KimYong Soo Lee
Dec 18, 2003·Neurobiology of Disease·Elizabeth A LeuchtmannJohn W McDonald
Jun 25, 2002·The Annals of Thoracic Surgery·Caroline C MenacheJane W Newburger
Nov 9, 2000·European Journal of Pharmacology·H IkesueR Oishi
Aug 24, 1999·Neurochemistry International·N Marks, M J Berg
May 29, 2003·Pediatric Neurology·Nuno Lobo Antunes
Apr 20, 1999·Pediatric Neurology·N L AntunesE Lis
Apr 5, 2003·Molecular and Cellular Neurosciences·Malgorzata Zawadzka, Bozena Kaminska
Nov 8, 2001·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·E F Wijdicks
Aug 11, 2001·The New England Journal of Medicine·C M Filley, B K Kleinschmidt-DeMasters
Apr 5, 2011·Therapeutic Hypothermia and Temperature Management·George LotockiHelen M Bramlett
Mar 17, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A N MurphyM F Beal
Jul 22, 1998·Epilepsia·E TaubøllL Gjerstad
Jun 22, 2006·International Journal of Hematology·Nobuharu FujiiMitsune Tanimoto
Jul 10, 2003·Lancet Neurology·Christopher HalfpennyNeil Scolding
Nov 1, 2011·Cutaneous and Ocular Toxicology·Francisco J AscasoJosé A Cristóbal
Nov 30, 2010·Journal of the Neurological Sciences·Sriram VennetiLaura J Balcer
Jul 6, 2007·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·P AmodioA Gatta
Feb 21, 2004·British Journal of Pharmacology·Anna Maria CanudasMercè Pallàs
Oct 26, 2011·Pediatric Transplantation·Rosa CuiAbraham Shaked
Sep 10, 2004·Progress in Histochemistry and Cytochemistry·Rita Rezzani
Sep 15, 2004·European Journal of Pharmacology·Michihiro MurozonoYasuo Watanabe
Oct 31, 1998·Brain Research·T A SeatonA H Schapira
Sep 12, 2015·Seminars in Nephrology·Girish Mour, Christine Wu
Oct 14, 2009·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Pere BarbaJorge Sierra

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis