Marcellus Kristen A, Bugiel Steven, Nunnikhoven Andrée, Curran Ivan, Gill Santokh S
Regulatory Toxicology Research Division, Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, ON K1A 0K9, Canada.
Nanomaterials (Basel). 2024 Feb 27;14(5):429. doi: 10.3390/nano14050429.
Microplastics are considered an emerging environmental pollutant due to their ubiquitous presence in the environment. However, the potential impact of microplastics on human health warrants further research. Recent studies have reported neurobehavioral and neurotoxic effects in marine and rodent models; however, their impact on the underlying cellular physiology in mammals remains unclear. Herein, we exposed neural stem cells and neural stem cell-derived astrocytes, oligodendrocytes, and neurons to various sizes and concentrations of polystyrene nano- and microplastics. We investigated their cellular uptake, impact on cytotoxicity, and alteration of gene expression through transcriptome profiling. The cell type most affected by decreased viability were astrocytes after 7 days of repeated exposure. Transcriptional analysis showed that 1274 genes were differentially expressed in astrocytes exposed to 500 nm microplastics, but only 531 genes were altered in astrocytes exposed to 50 nm nanoplastics. Both canonical pathway and Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated pathways were involved in neuroinflammation, innate and adaptive immunity, cell migration, proliferation, extracellular matrix remodeling, and cytoskeleton structures. The downregulated pathways were involved in lipid metabolism, specifically fatty acid oxidation and cholesterol metabolism. Our results show that neural stem cell-derived astrocytes repeatedly exposed to nano- and microplastics for 7 days undergo changes that are hallmarks of astrogliosis.
由于微塑料在环境中普遍存在，它们被认为是一种新出现的环境污染物。然而，微塑料对人类健康的潜在影响值得进一步研究。最近的研究报道了在海洋和啮齿动物模型中的神经行为和神经毒性作用；然而，它们对哺乳动物潜在细胞生理学的影响仍不清楚。在此，我们将神经干细胞以及神经干细胞衍生的星形胶质细胞、少突胶质细胞和神经元暴露于不同大小和浓度的聚苯乙烯纳米塑料和微塑料中。我们通过转录组分析研究了它们的细胞摄取、对细胞毒性的影响以及基因表达的改变。反复暴露7天后，活力下降最受影响的细胞类型是星形胶质细胞。转录分析表明，暴露于500纳米微塑料的星形胶质细胞中有1274个基因差异表达，但暴露于50纳米纳米塑料的星形胶质细胞中只有531个基因发生改变。经典通路分析和京都基因与基因组百科全书分析均表明，上调的通路涉及神经炎症、固有免疫和适应性免疫、细胞迁移、增殖、细胞外基质重塑和细胞骨架结构。下调的通路涉及脂质代谢，特别是脂肪酸氧化和胆固醇代谢。我们的结果表明，反复暴露于纳米塑料和微塑料7天的神经干细胞衍生的星形胶质细胞会发生变化，这些变化是星形胶质细胞增生的特征。
