کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2201650 1100031 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Neuroprotective effects of steroid analogues on P19-N neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Neuroprotective effects of steroid analogues on P19-N neurons
چکیده انگلیسی

Naturally occurring neurosteroids are potent allosteric modulators of γ-aminobutyric acidA receptor and through augmentation of γ-aminobutyric acidA receptor function, can protect neuronal cells against N-methyl-d-aspartate receptor over-activation, ischemia and traumatic brain injury. In this study, mouse P19 cells were induced to differentiate into post-mitotic neurons and were subjected to excitotoxicity in the presence of N-methyl-d-aspartate. Novel synthetic analogues of the endogenous neurosteroids allopregnanolone and dehydroepiandrostrone, inhibited excitotoxic cell death of P19-N neurons, by directly maintaining the activation of PKB/Akt kinase and interfering with the intrinsic mitochondrial apoptotic pathway, preserving cytochrome c in the mitochondria and Bax in the cytoplasm. The efficiency and the potency of these neurosteroids were similar to those of allopregnanolone and dehydroepiandrostrone. Their effects were γ-aminobutyric acidA receptor mediated, since they were abolished in the presence of bicuculline, an antagonist of receptor's function. In addition, the synthetic compounds retained the ability to alter γ-aminobutyric acidA receptor subunit gene expression, but their effects on transcriptional activity were less pronounced than those of allopregnanolone and dehydroepiandrostrone. These results suggest that synthetic neurosteroids may serve as potent, membrane acting, neuroprotectants against N-methyl-d-aspartate receptor neurotoxicity on neuronal cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 50, Issue 4, March 2007, Pages 660–670
نویسندگان
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