Maternal exposure to nanopolystyrene induces neurotoxicity in offspring through P53-mediated ferritinophagy and ferroptosis in the rat hippocampus

神经毒性 后代 海马体 神经科学 化学 生物 医学 内科学 怀孕 毒性 遗传学
作者
Jiang Chen,Licheng Yan,Yaping Zhang,Xuan Liu,Ying Wei,Yiming Zhao,Kang Li,Yue Shi,Huanliang Liu,Wenqing Lai,Lei Tian,Bencheng Lin
出处
期刊:Journal of Nanobiotechnology [BioMed Central]
卷期号:22 (1) 被引量:7
标识
DOI:10.1186/s12951-024-02911-9
摘要

There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring.
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