DOI: 10.1002/ana.410400511. Cyclosporine induces neuronal apoptosis and selective oligodendrocyte death in cortical cultures

Cyclosporine induces neuronal apoptosis and selective oligodendrocyte death in cortical cultures

10.1002/ana.410400511

Crossref journal-article

Wiley

Annals of Neurology (311)

Abstract

AbstractCyclosporine is used clinically as an immunosuppressant, but carries a risk of central nervous system toxicity due to undefined mechanisms. We examined the abiility of cyclosporine expsure to kill cultured mouse cortical neurons and glia. Mixed neuron/glial cultures exposed to 1 to 20 μM cyclosporine for 24 to 48 hours developed concentration‐dependent neuronal death, with most neurons destroyed by 20 μM cyclosporine. This Neuronal death was characterized by cell body shrinkage and bleebbing, chromatin condenstation, 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 deoxyuridinetriphosphate‐biotin nick end‐labeling) staining and was attenuatd by application of ciliary neurotrophic factor or insulin‐like growth factor I but not glutamate receptro 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.

Bibliography

McDonald, J. W., Goldberg, M. P., Gwag, B. J., Chi, S., & Choi, D. W. (1996). Cyclosporine induces neuronal apoptosis and selective oligodendrocyte death in cortical cultures. Annals of Neurology, 40(5), 750â758. Portico.

Authors 5

John W. McDonald (first)
Mark P. Goldberg (additional)
Byoung J. Gwag (additional)
Shu‐Ing Chi (additional)
Dennis W. Choi (additional)

References 57 Referenced 109

10.1056/NEJM198912213212507
10.2165/00003495-199040030-00001
10.1136/bmj.302.6767.4
10.1016/S0140-6736(85)92053-7
10.1056/NEJM198710013171404
10.1016/S0733-8619(18)30869-7
10.1056/NEJM198402233100814
10.1136/bmj.290.6462.139
10.1212/WNL.37.6.1072
{'key': 'e_1_2_1_10_2', 'first-page': '393', 'article-title': 'Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin. Bone Marrow transplant patients receiving cyclosporin', 'volume': '8', 'author': 'Reece DE', 'year': '1991', 'journal-title': 'Bone Marrow Transplant'} / Bone Marrow Transplant / Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin. Bone Marrow transplant patients receiving cyclosporin by Reece DE (1991)
10.1002/ana.410360503
10.1212/WNL.45.11.1962
10.1016/S0140-6736(84)91556-3
{'key': 'e_1_2_1_14_2', 'first-page': '147', 'article-title': 'Cortical blindness: a rare complication of cyclosporin therapy', 'volume': '6', 'author': 'Ghalie R', 'year': '1990', 'journal-title': 'Bone Marrow Transplant'} / Bone Marrow Transplant / Cortical blindness: a rare complication of cyclosporin therapy by Ghalie R (1990)
10.1056/NEJM199008093230616
{'key': 'e_1_2_1_16_2', 'first-page': '651', 'article-title': 'MR imaging of reversible cyclosporin A‐induced neurotoxicity', 'volume': '12', 'author': 'Truwit CL', 'year': '1991', 'journal-title': 'AJNR'} / AJNR / MR imaging of reversible cyclosporin A‐induced neurotoxicity by Truwit CL (1991)
{'key': 'e_1_2_1_17_2', 'first-page': '899S', 'article-title': 'Hyperintense cortex in proton‐density weighted images: a new MRI sign in cyclosporin‐A‐induced encephalopathy after liver transplantation', 'volume': '45', 'author': 'Jansen O', 'year': '1995', 'journal-title': 'J Neurology'} / J Neurology / Hyperintense cortex in proton‐density weighted images: a new MRI sign in cyclosporin‐A‐induced encephalopathy after liver transplantation by Jansen O (1995)
10.1259/0007-1285-66-783-271
{'key': 'e_1_2_1_19_2', 'first-page': '3181', 'article-title': 'Torre‐Cisneros J. Neuropathologic findings in liver transplantation: a comparative study of cyclosporine and FK‐506', 'volume': '23', 'author': 'Lopez OL', 'year': '1991', 'journal-title': 'Transplant Proc'} / Transplant Proc / Torre‐Cisneros J. Neuropathologic findings in liver transplantation: a comparative study of cyclosporine and FK‐506 by Lopez OL (1991)
10.1016/S0140-6736(88)92263-5
{'key': 'e_1_2_1_21_2', 'first-page': '77', 'article-title': 'Phosphorylated neurofilament accumulation in nuruonal perikarya by cyclopsorin A injection in rat brain', 'volume': '15', 'author': 'Tanaka T', 'year': '1993', 'journal-title': 'Methods Find Exp Clin Pharmacol'} / Methods Find Exp Clin Pharmacol / Phosphorylated neurofilament accumulation in nuruonal perikarya by cyclopsorin A injection in rat brain by Tanaka T (1993)
10.1097/00007890-198908000-00025
{'key': 'e_1_2_1_23_2', 'first-page': '179', 'article-title': 'Glia toxicity in dissociated cell cultures induced by cyclosporine', 'volume': '13', 'author': 'Stoltenburg‐Didinger G', 'year': '1992', 'journal-title': 'Neurotoxicology'} / Neurotoxicology / Glia toxicity in dissociated cell cultures induced by cyclosporine by Stoltenburg‐Didinger G (1992)
{'key': 'e_1_2_1_24_2', 'first-page': '307', 'article-title': 'Cyclosporin‐A induces apoptosis in cultured cortical neurons', 'volume': '38', 'author': 'McDonald JW', 'year': '1995', 'journal-title': 'Ann Neurol'} / Ann Neurol / Cyclosporin‐A induces apoptosis in cultured cortical neurons by McDonald JW (1995)
{'key': 'e_1_2_1_25_2', 'first-page': '751', 'article-title': 'Cyclosporin‐A induces apoptosis in cultured cortical neurons', 'volume': '21', 'author': 'McDonald JW', 'year': '1995', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Cyclosporin‐A induces apoptosis in cultured cortical neurons by McDonald JW (1995)
{'key': 'e_1_2_1_26_2', 'first-page': '1317', 'article-title': 'Cyclosporin exposure is cytotoxic to cultured cortical neurons', 'volume': '19', 'author': 'Chi S‐I', 'year': '1993', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Cyclosporin exposure is cytotoxic to cultured cortical neurons by Chi S‐I (1993)
{'key': 'e_1_2_1_27_2', 'first-page': '46', 'volume-title': 'In vitro biological methods, methods in toxicology', 'author': 'Rose K', 'year': '1992'} / In vitro biological methods, methods in toxicology by Rose K (1992)
10.1016/0165-0270(87)90041-0
10.1038/348334a0
10.1083/jcb.119.3.493
10.1038/bjc.1972.33
10.1146/annurev.ne.16.030193.000335
10.1083/jcb.106.3.829
10.1046/j.1471-4159.1995.65031395.x
{'key': 'e_1_2_1_35_2', 'first-page': '116', 'article-title': 'Cyclosporine neurotoxicity in liver transplant recipeints: report of three cases', 'volume': '20', 'author': 'Deierhoi MH', 'year': '1988', 'journal-title': 'Transplant Proc'} / Transplant Proc / Cyclosporine neurotoxicity in liver transplant recipeints: report of three cases by Deierhoi MH (1988)
10.1016/0006-8993(86)91381-8
10.1038/358584a0
{'issue': '1', 'key': 'e_1_2_1_38_2', 'first-page': '2398', 'article-title': 'Effect of cyclosporine on prostacyclin synthesis by vascular tissue in rabbits', 'volume': '15', 'author': 'Neild GH', 'year': '1983', 'journal-title': 'J Transplant Proc'} / J Transplant Proc / Effect of cyclosporine on prostacyclin synthesis by vascular tissue in rabbits by Neild GH (1983)
{'issue': '1', 'key': 'e_1_2_1_39_2', 'article-title': 'Cyclosporin‐syndrome post bone marrow tranplantation: interference with vascular prostacyclin production', 'volume': '64', 'author': 'Boogaerts MA', 'year': '1984', 'journal-title': 'Blood'} / Blood / Cyclosporin‐syndrome post bone marrow tranplantation: interference with vascular prostacyclin production by Boogaerts MA (1984)
{'key': 'e_1_2_1_40_2', 'first-page': '789', 'article-title': 'Cyclosporine‐associated cenral nervous system toxicity', 'volume': '318', 'author': 'de groen PC', 'year': '1988', 'journal-title': 'N Engl J Med'} / N Engl J Med / Cyclosporine‐associated cenral nervous system toxicity by de groen PC (1988)
10.1002/jnr.490380113
10.1126/science.7725105
{'key': 'e_1_2_1_43_2', 'first-page': '2122', 'article-title': 'Drug‐induced apoptosis is not necessarily dependetn on macromolecular synthesis or proliferation in the p53‐negative human prostate cancer cell line PC‐3', 'volume': '55', 'author': 'Borner MM', 'year': '1995', 'journal-title': 'Cancer Res'} / Cancer Res / Drug‐induced apoptosis is not necessarily dependetn on macromolecular synthesis or proliferation in the p53‐negative human prostate cancer cell line PC‐3 by Borner MM (1995)
{'key': 'e_1_2_1_44_2', 'first-page': '357', 'article-title': 'Regional distribution of calcium/calmodulin‐dependent phosphatase activity of calcineurin in rat brain', 'volume': '64', 'author': 'Chung E', 'year': '1989', 'journal-title': 'Res Commun Chem Pathol Pharmacol'} / Res Commun Chem Pathol Pharmacol / Regional distribution of calcium/calmodulin‐dependent phosphatase activity of calcineurin in rat brain by Chung E (1989)
{'key': 'e_1_2_1_45_2', 'first-page': '357', 'article-title': 'Inhibition by cyclosporin A of a Ca2+‐dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress', 'volume': '255', 'author': 'Crompton M', 'year': '1988', 'journal-title': 'Biochem J'} / Biochem J / Inhibition by cyclosporin A of a Ca2+‐dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress by Crompton M (1988)
10.1038/ki.1988.170
10.1016/0006-2952(93)90491-E
10.1016/0008-8749(87)90296-6
10.1016/0006-8993(92)91465-Q
10.1073/pnas.90.21.9808
10.1016/0304-3940(93)90511-I
10.1016/0006-8993(94)91138-X
10.1038/371336a0
10.1038/339625a0
10.1016/0014-5793(92)80616-O
10.1006/jmcc.1993.1162
10.1006/exnr.1995.1074

Dates

Type	When
Created	20 years, 8 months ago (Jan. 1, 2005, 9:52 a.m.)
Deposited	1 year, 10 months ago (Oct. 26, 2023, 11:54 a.m.)
Indexed	3 months, 2 weeks ago (May 20, 2025, 10:29 a.m.)
Issued	28 years, 10 months ago (Nov. 1, 1996)
Published	28 years, 10 months ago (Nov. 1, 1996)
Published Online	20 years, 10 months ago (Oct. 8, 2004)
Published Print	28 years, 10 months ago (Nov. 1, 1996)

Funders 0

None

BibTeX

@article{McDonald_1996, title={Cyclosporine induces neuronal apoptosis and selective oligodendrocyte death in cortical cultures}, volume={40}, ISSN={1531-8249}, url={http://dx.doi.org/10.1002/ana.410400511}, DOI={10.1002/ana.410400511}, number={5}, journal={Annals of Neurology}, publisher={Wiley}, author={McDonald, John W. and Goldberg, Mark P. and Gwag, Byoung J. and Chi, Shu‐Ing and Choi, Dennis W.}, year={1996}, month=nov, pages={750–758} }

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