کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8552774 | 1562274 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together
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کلمات کلیدی
Embryonic neural stem cellsNSCGFAPTerbutalineβARDAPIMAP24′,6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceDexamethasone - دگزامتازونPreterm labor - زایمان زودرسPC12 cells - سلول های PC12Neural stem cell - سلول های بنیادی عصبیC6 cells - سلولهای C6Developmental neurotoxicity - عصبی رشدیGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالmicrotubule-associated protein 2 - پروتئین مرتبط با میکروتوبول 2β-Adrenergic receptor - گیرنده β-adrenergic
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in increased risk of neurodevelopmental disorders. We used a variety of cell models to establish the critical stages at which neurodifferentiation is vulnerable to these agents and to determine whether combined exposures produce a worsened outcome. Terbutaline selectively promoted the initial emergence of glia from embryonic neural stem cells (NSCs). The target for terbutaline shifted with developmental stage: at later developmental stages modeled with C6 and PC12 cells, terbutaline had little effect on glial differentiation (C6 cells) but impaired the differentiation of neuronotypic PC12 cells into neurotransmitter phenotypes. In contrast to the specificity shown by terbutaline, dexamethasone affected both neuronal and glial differentiation at all stages, impairing the emergence of both cell types in NSCs but with a much greater impairment for glia. At later stages, dexamethasone promoted glial cell differentiation (C6 cells), while shifting neuronal cell differentiation so as to distort the balance of neurotransmitter phenotypes (PC12 cells). Finally, terbutaline and dexamethasone interacted synergistically at the level of late stage glial cell differentiation, with dexamethasone boosting the ability of terbutaline to enhance indices of glial cell growth and neurite formation while producing further decrements in glial cell numbers. Our results support the conclusion that terbutaline and dexamethasone are directly-acting neuroteratogens, and further indicate the potential for their combined use in preterm labor to worsen neurodevelopmental outcomes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volumes 400â401, 1 May 2018, Pages 57-64
Journal: Toxicology - Volumes 400â401, 1 May 2018, Pages 57-64
نویسندگان
Theodore A. Slotkin, Samantha Skavicus, Frederic J. Seidler,