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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >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

机译：米非司酮（RU486）保护浦肯野细胞免于出生后大鼠和小鼠小脑的器官切片培养物中的细胞死亡

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摘要

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 muM) 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(Nes/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. [References: 18]
机译：米非司酮（RU486）与孕激素和糖皮质激素受体（PR和GR）都具有高亲和力结合，因其可用于终止意外怀孕而广为人知，但已提出其他活性，包括神经保护作用。研究了出生后3至7天的大鼠（P3-P7）的小脑器官型培养物，以研究RU486的神经保护潜力。在这种培养物中，浦肯野细胞进入凋亡过程，P3最高。这项研究表明，RU486（20μM）可以保护浦肯野细胞免受这种凋亡过程的影响。神经保护作用的确不涉及PR或GR，因为它不能被这些受体的其他配体模仿或抑制，并且因为它仍然发生在PR突变（PR-KO）小鼠和脑特异性GR突变小鼠（GR）中（Nes / Cre））。强大的抗氧化剂不能阻止浦肯野细胞从这种发育中的细胞死亡。 RU486的神经保护作用还可以在病理性浦肯野细胞死亡中观察到。的确，这种类固醇能够防止浦肯野细胞变性（pcd）突变小鼠（遗传性神经退行性共济失调的小鼠模型）的小脑切片的器官型培养物中的浦肯野细胞死亡。在用RU486处理6天并进一步培养至21天的P0小脑切片中，合成类固醇的pcd / pcd Purkinje细胞存活率提高了16.2倍。我们的结果表明，RU486可能通过尚未阐明的新机制来保护浦肯野细胞免于死亡。 [参考：18]

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