90 / 2023-04-28 22:29:51

Neurotoxicity induced by combined exposure to polypropylene microplastics and DEHP in immature mice and the underlying molecular mechanism

polypropylene microplastics; DEHP; immature mice; neurotoxicity; combined effect

Abstract: Assessment of the health impacts of polypropylene microplastics (PP-MPs) to which infants and young children are easily exposed, is far from adequate. As a typical plasticizer used in plastic processing, di(2-ethylhexyl) phthalate (DEHP) is frequently found alongside microplastics in the ambient environment due to their concomitant circumstances. Studies have demonstrated that exposure to either microplastics or DEHP may induce neurotoxicity in animals, but their combined influence and the underlying molecular mechanisms have received less attention. This study examined how immature mice were affected by exposure to a combination of PP-MPs and DEHP by neuroethology, histopathology and biomarker detection. The results showed that exposure to PP-MPs and/or DEHP did induce neurotoxic effects in the immature mice, including neurocognitive deficits and hippocampal impairments. The severity of the neurotoxicity increased with increasing concentrations of PP-MPs, furthermore, combined exposure to PP-MPs and DEHP exhibited additive or synergistic effects compared with PP-MPs or DEHP individually. Transcriptomic analyses revealed that the PP-MPs and/or DEHP exposure altered the expression profiles of gene clusters involved in the stress response, and protein processing in endoplasmic reticulum. Quantitative analyses further indicated that PP-MPs and/or DEHP exposure inhibited the activity of the heat shock response mediated by HSF1, while chronically activated the unfolded protein response, consequently inducing neurotoxicity through neuronal apoptosis in the immature mice. This study highlights the neurotoxicity caused by combined exposure to PP-MPs and DEHP in immature mice, and provides new insights that can be used to help protect the health of young children.