کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5858953 | 1562318 | 2015 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos
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کلمات کلیدی
βAROrganophosphate pesticides - آفت کش های ارگانوفسفاتanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceDexamethasone - دگزامتازونgestational day - روز بارداریpostnatal day - روز پس از زایمانCerebellum - مخچهnorepinephrine - نوراپی نفرینNicotine - نیکوتین Chlorpyrifos - کلرپیریفوسβ-Adrenergic receptor - گیرنده β-adrenergic
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3 mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1 mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2 mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 338, 2 December 2015, Pages 8-16
Journal: Toxicology - Volume 338, 2 December 2015, Pages 8-16
نویسندگان
Theodore A. Slotkin, Samantha Skavicus, Frederic J. Seidler,