Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes

Simon J. Hawkins, Lucy A. Crompton, Aman Sood, Margaret Saunders, Noreen T. Boyle, Amy Buckley, Aedín M. Minogue, Sarah F. McComish, Natalia Jiménez-Moreno, Oscar Cordero-Llana, Petros Stathakos, Catherine E. Gilmore, Stephen Kelly, Jon D. Lane, C. Patrick Case, Maeve A. Caldwell*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

57 Citations (Scopus)
493 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)427-433
Number of pages7
JournalNature Nanotechnology
Early online date2 Apr 2018
Publication statusPublished - 2 Apr 2018

Bibliographical note

Significant contribution by JDL and members of the Lane lab (LC; PS; NJ-M).

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