Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes
Autor: | Amy M. Buckley, Lucy A. Crompton, Aedín M. Minogue, Catherine E. Gilmore, Simon J. Hawkins, Natalia Jiménez-Moreno, Jon D. Lane, Stephen Kelly, Margaret Saunders, Maeve A. Caldwell, Petros Stathakos, Oscar Cordero-Llana, C. Patrick Case, Noreen T. Boyle, Aman Sood, Sarah F. McComish |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male DNA damage Placenta Biomedical Engineering Developmental toxicity Bioengineering 02 engineering and technology Models Biological Cell Line 03 medical and health sciences Mice In vivo Pregnancy medicine Animals Humans General Materials Science Electrical and Electronic Engineering Neurons Chemistry Autophagy 021001 nanoscience & nanotechnology Condensed Matter Physics medicine.disease Atomic and Molecular Physics and Optics Neural stem cell Astrogliosis Cell biology Pregnancy Complications 030104 developmental biology Cell culture Neurodevelopmental Disorders Astrocytes Toxicity Nanoparticles Female Neurotoxicity Syndromes 0210 nano-technology |
Zdroj: | Hawkins, S J, Crompton, L A, Sood, A, Saunders, M, Boyle, N T, Buckley, A, Minogue, A M, McComish, S F, Jiménez-Moreno, N, Cordero-Llana, O, Stathakos, P, Gilmore, C E, Kelly, S, Lane, J D, Case, C P & Caldwell, M A 2018, ' Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes ', Nature Nanotechnology, vol. 13, pp. 427-433 . https://doi.org/10.1038/s41565-018-0085-3 |
DOI: | 10.1038/s41565-018-0085-3 |
Popis: | The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes. Crucially, neuronal DNA damage is mediated by astrocytes. Inhibiting the autophagic degradation in the BeWo barrier by overexpression of the dominant-negative human ATG4BC74A significantly reduces the levels of DNA damage in astrocytes. In vivo, indirect NP toxicity in mice results in neurodevelopmental abnormalities with reactive astrogliosis and increased DNA damage in the fetal hippocampus. Our results demonstrate the potential importance of autophagy to elicit NP toxicity and the risk of indirect developmental neurotoxicity after maternal NP exposure. |
Databáze: | OpenAIRE |
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