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Dufresne, J.

Publications and source records attributed to Dufresne, J..

2 recordsLinked to original sources

EFFECTS OF SUBCHRONIC EXPOSURE TO POLYSTYRENE NANOPLASTICS ON THE MOUSE INTESTINE

Nanoplastics (NPs) are being used increasingly in cosmetics, personal care products, foods, automotive products, and cleaning products, as well as being by-products of some industrial processes. The aim of this study was to examine the effects of a sub-chronic exposure of NPs on various biological systems, using mice as a model. Adult male mice were administered 500 nm polystyrene (PS) NPs at 0.15 mg/day and 1.5 mg/day, to mimic subchronic exposure to NPs. Control mice were gavaged in the same manner but with sterile water instead of NPs. The mice were weighed weekly and treated daily for 60 days. The mice were then euthanized, and multiple tissues were retrieved and fixed or frozen for subsequent analyses. The intestines were rinsed and divided into pieces of the three regions: duodenum, jejunum, and ileum. Hematoxylin and eosin (H&E) staining was performed to evaluate histopathology, and RNA-Seq was conducted on tissues from all three regions. H&E staining revealed few effects on the duodenum, but increasingly pronounced disruption and epithelial alterations in the jejunum and ileum, respectively. RNA-Seq analysis of controls compared to the high-dose (HD; 1.5 mg/day) group supported these observations. The number of differentially expressed genes (DEGs) was low (19) in the duodenum, higher in the jejunum (114 DEGs), and significantly greater in the ileum (4982 DEGs). Genes associated with immune response, ion transport, and junctional proteins were among the groups of genes most differentially expressed. These results demonstrate the potentially harmful effects of PS NPs on the intestinal system of mice.

pharmacology and toxicology↗

Polystyrene Nanoplastics Accumulate in Murine Cortex and Induce Transient Microglial Activation via Endolysosomal Retention

Environmental degradation and accumulation of plastics results in micro- and nanoplastics (MNPLs) that are small enough to cross biological barriers, including the blood-brain barrier. Microglia, resident immune cells of brain, are critical regulators of neuroimmune homeostasis and represent a cellular target of nanoplastic exposure. In this study, we assessed the neurotoxic effects of two sizes of polystyrene nanoplastics (PS-NPs; 100 nm and 500 nm) using integrated in vivo and in vitro exposure and washout paradigms. In vivo exposure in mice (60 days; 0.15 or 1.5 mg/day) showed the accumulation of both PS-NP sizes in the cerebral cortex without histopathological damage. However, cortical microglia showed pronounced morphological remodeling, observed as increased expression of Iba1 and GFAP. Transcriptomic profiling of cortical tissue revealed a strong size-dependent response. The 100 nm PS-NP group revealed 18 DEGs (|log2FC| [&ge;] 2, padj < 0.05), whereas the 500 nm PS-NPs showed more than 4,000 DEGs, including upregulation of immune- and microglia-associated genes (CCL5, CXCL10, LCN2, LYZ2) and downregulation of synaptic and neuronal signaling genes (GRIN2B, SYN1, STX1B, MAP1B, ITPR1/2). In vitro assessment, using BV2 microglia cells, showed internalization of PS-NPs via the endolysosomal pathway, with strong co-localization to Rab7- and LAMP2-positive compartments and prolonged intracellular retention following exposure washout. Also, microglial activation markers (Iba1, CD68) exhibited a transient, size- and concentration-dependent increase, correlated with intracellular particle burden rather than cumulative exposure. Overall, these findings demonstrate that PS-NPs accumulate in brain, driving size-dependent microglia activation and transcriptomic reprogramming, even after cessation of exposure to PS-NPs. HighlightsO_LIPS-NPs (100 nm and 500 nm) reach mouse cerebral cortex following 60-day oral exposure. C_LIO_LIPS-NPs were internalized by microglia; accumulated in endolysosomal compartments. C_LIO_LIPS-NP exposure induced transient microglial activation without sustained cytotoxicity. C_LIO_LIMicroglial activation was correlated with intracellular PS-NPs burden. C_LIO_LITranscriptomics revealed disruption of neuroimmune and microglial regulatory pathways. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/712727v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@466df4org.highwire.dtl.DTLVardef@1dcb163org.highwire.dtl.DTLVardef@21916org.highwire.dtl.DTLVardef@1bcf775_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗