Alleviation of neurotoxicity induced by polystyrene nanoplastics by increased exocytosis from neurons

• Published in: Biochemical and biophysical research communications Vol. 668; pp. 19 - 26
• Main Authors: Han, Seung-Woo, Kim, Taek-Yeong, Bae, Jin-Sil, Choi, Jinhee, Ryu, Kwon-Yul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.08.2023
• Subjects: Animals; Exocytosis; Fibroblasts; Humans; Inflammation; Mice; Microplastics; Nanoparticles - toxicity; Nanoplastics; Neurons; Oxidative stress; Polystyrenes - toxicity; Retrograde transport; Water Pollutants, Chemical; NPs; Oxidative stress; PS; Inflammation; Exocytosis; Retrograde transport; HDAC6; Nanoplastics
• DOI: 10.1016/j.bbrc.2023.05.070
• ISSN: 0006-291X

Nanoplastics (NPs) are potentially toxic and pose a health risk as they can induce an inflammatory response and oxidative stress at cellular and organismal levels. Humans can be exposed to NPs through various routes, including ingestion, inhalation, and skin contact. Notably, uptake into the body via inhalation could result in brain accumulation, which may occur directly across the blood-brain barrier or via other routes. NPs that accumulate in the brain may be endocytosed into neurons, inducing neurotoxicity. Recently, we demonstrated that exposure to polystyrene (PS)-NPs reduces the viability of neurons. We have also reported that inhibiting the retrograde transport of PS-NPs by histone deacetylase 6 (HDAC6) prevents their intracellular accumulation and promotes their export in mouse embryonic fibroblasts. However, whether HDAC6 inhibition can improve neuronal viability by increasing exocytosis of PS-NPs from neurons remains unknown. In this study, mice were intranasally administered fluorescent PS-NPs (PS-YG), which accumulated in the brain and showed potential neurotoxic effects. In cultured neurons, the HDAC6 inhibitor ACY-1215 reduced the fluorescence signal detected from PS-YG, suggesting that the removal of PS-YG from neurons was promoted. Therefore, these results suggest that blocking the retrograde transport of PS-NPs using an HDAC6 inhibitor can alleviate the neurotoxic effects of PS-NPs that enter the brain. •Intranasal administration of PS-NPs causes their accumulation in the mouse brain.•PS-NP accumulation in the mouse brain induces acute neurotoxic effects.•HDAC6 inhibition results in the rapid export of PS-NPs from neurons by exocytosis.•The rapid export of PS-NPs from neurons alleviates neurotoxic effects of PS-NPs.•The rapid export of PS-NPs from neurons reduces oxidative stress induced by PS-NPs.