NDLI: Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum

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Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum

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Mifepristone (RU486) protects Purkinje cells from cell death in organotypic slice cultures of postnatal rat and mouse cerebellum

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Schumacher, M. Baulieu, E-e El-etr, M. Dusart, I. Ghoumari, A. M. Sotelo, C. Tronche, F.
Description	Author Affiliation: Ghoumari AM ( Institut National de la Santé et de la Recherche Médicale U488, Batiment Gregory Pincus, 80 Rue du Général Leclerc, 94276 Kremlin-Bicêtre, France. ghoumari@kb.inserm.fr);
Abstract	Mifepristone (RU486), which binds with high affinity to both progesterone and glucocorticosteroid receptors (PR and GR), is well known for its use in the termination of unwanted pregnancy, but other activities including neuroprotection have been suggested. Cerebellar organotypic cultures from 3 to 7 postnatal day rat (P3-P7) were studied to examine the neuroprotective potential of RU486. In such cultures, Purkinje cells enter a process of apoptosis with a maximum at P3. This study shows that RU486 (20 microM) can protect Purkinje cells from this apoptotic process. The neuroprotective effect did involve neither PR nor GR, because it could not be mimicked or inhibited by other ligands of these receptors, and because it still took place in PR mutant (PR-KO) mice and in brain-specific GR mutant mice (GRNes/Cre). Potent antioxidant agents did not prevent Purkinje cells from this developmental cell death. The neuroprotective effect of RU486 could also be observed in pathological Purkinje cell death. Indeed, this steroid is able to prevent Purkinje cells from death in organotypic cultures of cerebellar slices from Purkinje cell degeneration (pcd) mutant mice, a murine model of hereditary neurodegenerative ataxia. In P0 cerebellar slices treated with RU486 for 6 days and further kept in culture up to 21 days, the synthetic steroid increased by 16.2-fold the survival of pcd/pcd Purkinje cells. Our results show that RU486 may act through a new mechanism, not yet elucidated, to protect Purkinje cells from death.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cerebellum Pathology Hormone Antagonists Pharmacology Mifepristone Purkinje Cells Drug Effects Animals Animals, Newborn Antioxidants Brain Cell Death Cell Division Cell Survival Metabolism Corticosterone Ligands Mice Mice, Knockout Mice, Mutant Strains Neurons Organ Culture Techniques Radioimmunoassay Rats, Sprague-Dawley Time Factors Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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