دورية أكاديمية
Characterization of Developmental neurotoxicity of As, Cd and Pb mixture: Synergistic Action of Metal Mixture in Glial and Neuronal Functions
| العنوان: | Characterization of Developmental neurotoxicity of As, Cd and Pb mixture: Synergistic Action of Metal Mixture in Glial and Neuronal Functions |
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| المؤلفون: | Rai, Asit, Maurya, Shailendra Kr, Khare, Priyanka, Shrivastava, Abhinav, Bandyopadhyay, Sanghamitra |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2010 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Neurotoxicology |
| الوصف: | The neurotoxicity of individual metals is well-investigated but that of metal mixture (MM), an environmental reality, in the developing brain is relatively obscure. We investigated the combinatorial effect of As, Cd and Pb on rat brain development, spanning in utero to postnatal development. MM was administered by gavage to pregnant and lactating rats, and to post-weaning pups till 2-months. The pups exhibited behavioral disturbances characterized by hyperlocomotion, increased grip strength and learning-memory deficit. Disruption of the blood brain barrier (BBB) was associated with dose-dependent increase in deposition of the metals in developing brain. Astrocytes were affected by MM treatment as evident from their reduced density, area, perimeter, compactness and number of processes, and increased apoptosis in cerebral cortex and cerebellum. The metals induced synergistic reduction in glial fibrillary acidic protein (GFAP) expression during brain development; however, post-weaning withdrawal of MM partially restored the levels of GFAP in adults. To characterize the toxic mechanism we treated rat primary astrocytes with MM at concentrations ranging from lethal concentration (LC) 10 to LC 75 of the metals. We observed synergistic down-regulation in viability and increase in apoptosis of the astrocytes that was induced by proximal activation of ERK signalling, and down-stream activation of JNK pathway. Further, rise in [Ca2+] i and ROS generation promoted apoptosis in the astrocytes. Taken together, these observations are the first to show that mixture of As, Cd and Pb has the capacity to induce synergistic toxicity in astrocytes that may compromise the BBB, and may cause behaviroal dysfunction in developing rats. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://toxsci.oxfordjournals.org/cgi/content/short/kfq266v1Test; http://dx.doi.org/10.1093/toxsci/kfq266Test |
| DOI: | 10.1093/toxsci/kfq266 |
| الإتاحة: | https://doi.org/10.1093/toxsci/kfq266Test http://toxsci.oxfordjournals.org/cgi/content/short/kfq266v1Test |
| حقوق: | Copyright (C) 2010, Society of Toxicology |
| رقم الانضمام: | edsbas.A5D5BAD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/toxsci/kfq266 |
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