{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:03:50Z","timestamp":1792674230168,"version":"4.5.0"},"reference-count":18,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,6,24]]},"abstract":"<jats:p>\n                    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\u2014P7) 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 \u03bcM) 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  (GR\n                    <jats:sup>Nes\/Cre<\/jats:sup>\n                    ). 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\n                    <jats:italic>Purkinje cell degeneration<\/jats:italic>\n                    (\n                    <jats:italic>pcd<\/jats:italic>\n                    )  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\n                    <jats:italic>pcd<\/jats:italic>\n                    \/\n                    <jats:italic>pcd<\/jats:italic>\n                    Purkinje cells. Our results show that RU486 may act  through a new mechanism, not yet elucidated, to protect Purkinje cells from  death.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1332667100","type":"journal-article","created":{"date-parts":[[2003,6,24]],"date-time":"2003-06-24T13:47:39Z","timestamp":1056462459000},"page":"7953-7958","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":69,"title":["Mifepristone (RU486) protects Purkinje cells from cell death in  organotypic slice cultures of postnatal rat and mouse cerebellum"],"prefix":"10.1073","volume":"100","author":[{"given":"A. M.","family":"Ghoumari","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U488, Batiment Gregory Pincus, 80 Rue du  G\u00e9n\u00e9ral Leclerc, 94276 Kremlin-Bic\u00eatre, France;  Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U106, Batiment de P\u00e9diatrie, 47 Boulevard de  l'H\u00f4pital, 75651 Paris Cedex 13, France; and  Centre National de la Recherche Scientifique FRE  2401, Coll\u00e8ge de France, 11 Place Marcelin Berthelot, 75005 Paris,  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Dusart","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U488, Batiment Gregory Pincus, 80 Rue du  G\u00e9n\u00e9ral Leclerc, 94276 Kremlin-Bic\u00eatre, France;  Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U106, Batiment de P\u00e9diatrie, 47 Boulevard de  l'H\u00f4pital, 75651 Paris Cedex 13, France; and  Centre National de la Recherche Scientifique FRE  2401, Coll\u00e8ge de France, 11 Place Marcelin Berthelot, 75005 Paris,  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"El-Etr","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U488, Batiment Gregory Pincus, 80 Rue du  G\u00e9n\u00e9ral Leclerc, 94276 Kremlin-Bic\u00eatre, France;  Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U106, Batiment de P\u00e9diatrie, 47 Boulevard de  l'H\u00f4pital, 75651 Paris Cedex 13, France; and  Centre National de la Recherche Scientifique FRE  2401, Coll\u00e8ge de France, 11 Place Marcelin Berthelot, 75005 Paris,  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Tronche","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U488, Batiment Gregory Pincus, 80 Rue du  G\u00e9n\u00e9ral Leclerc, 94276 Kremlin-Bic\u00eatre, France;  Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U106, Batiment de P\u00e9diatrie, 47 Boulevard de  l'H\u00f4pital, 75651 Paris Cedex 13, France; and  Centre National de la Recherche Scientifique FRE  2401, Coll\u00e8ge de France, 11 Place Marcelin Berthelot, 75005 Paris,  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Sotelo","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U488, Batiment Gregory Pincus, 80 Rue du  G\u00e9n\u00e9ral Leclerc, 94276 Kremlin-Bic\u00eatre, France;  Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U106, Batiment de P\u00e9diatrie, 47 Boulevard de  l'H\u00f4pital, 75651 Paris Cedex 13, France; and  Centre National de la Recherche Scientifique FRE  2401, Coll\u00e8ge de France, 11 Place Marcelin Berthelot, 75005 Paris,  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U488, Batiment Gregory Pincus, 80 Rue du  G\u00e9n\u00e9ral Leclerc, 94276 Kremlin-Bic\u00eatre, France;  Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U106, Batiment de P\u00e9diatrie, 47 Boulevard de  l'H\u00f4pital, 75651 Paris Cedex 13, France; and  Centre National de la Recherche Scientifique FRE  2401, Coll\u00e8ge de France, 11 Place Marcelin Berthelot, 75005 Paris,  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.-E.","family":"Baulieu","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U488, Batiment Gregory Pincus, 80 Rue du  G\u00e9n\u00e9ral Leclerc, 94276 Kremlin-Bic\u00eatre, France;  Institut National de la Sant\u00e9 et de la  Recherche M\u00e9dicale U106, Batiment de P\u00e9diatrie, 47 Boulevard de  l'H\u00f4pital, 75651 Paris Cedex 13, France; and  Centre National de la Recherche Scientifique FRE  2401, Coll\u00e8ge de France, 11 Place Marcelin Berthelot, 75005 Paris,  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,6,16]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2781282"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199003083221001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240350209"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01442.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00477-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-10-03710.1997"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00186.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03531.2002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/12703"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.1.208"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901770109"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(91)90128-M"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068912"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.3.8365352"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.18.2266"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)60500-2"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2000.118"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117551"}],"updated-by":[{"DOI":"10.1073\/pnas.1833959100","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2003,8,19]],"date-time":"2003-08-19T00:00:00Z","timestamp":1061251200000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1332667100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:11:44Z","timestamp":1649805104000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1332667100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,16]]},"references-count":18,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2003,6,24]]}},"alternative-id":["10.1073\/pnas.1332667100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1332667100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6,16]]},"assertion":[{"value":"2003-06-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}