Oral ingestion of polystyrene nanoplastics causes memory impairment and neuroinflammation by microglial uptake

Nanoplastics are produced by breakdown of plastics in environmental contamination or commercial use for cosmetics or daily expenses. Emerging evidence indicate that ingested nanoplastics with a size smaller than 100 nm have the potential to reach the brain and induces neurotoxicity. However, the potential toxicity of nanoplastics on brain are limited because of difficulties in synthesize of nanoplastics. In present study, we synthesized the fluorescent polystyrene nanoplastics (PSNPs) and examined the toxicity of PSNPs in brain in vivo and in vitro analyses by comparison to IR-813 fluorophore. Synthesized PSNPs were characterized by fluorescence imaging system, scanning electron microscopy, and Fourier-transform infrared spectroscopy. PSNPs were detected in adult mice brain by oral ingestion. In addition, a series of behavioral analyses showed that oral ingestion of PSNPs induced memory impairments. Among brain cells, PSNPs were predominantly internalized in microglia, and uptake of PSNPs induced microglial activation. In addition, the conditioned medium derived from microglia exposed to PSNPs repressed hippocampal neuronal activity. Furthermore, transcriptome analysis showed that PSNPs changed gene expressions in microglia, elevation of neuroinflammation in contrast to suppression of neurotrophic factors. These results indicated that predominant uptake of PSNPs in microglia induced elevation of neuroninflammatory responses whereas suppression of neurotrophic factors that may contribute to the cognitive impairment. Our findings indicate the toxic mechanism and potential detrimental effect of nanoplastic in brain and suggest a potential risk of cognitive impairment by exposure to nanoplastics.纳米塑料（Nanoplastics）可通过环境中塑料的降解，或是化妆品、日常消费品的商业应用过程中产生。越来越多的证据表明，粒径小于100纳米的摄入型纳米塑料可抵达大脑并诱发神经毒性。然而，由于纳米塑料的合成存在诸多技术难点，目前关于其对大脑的潜在毒性研究仍较为有限。本研究中，我们合成了荧光聚苯乙烯纳米塑料（Polystyrene Nanoplastics, PSNPs），并以IR-813荧光团为对照，通过体内与体外实验分析了PSNPs对大脑的毒性作用。我们通过荧光成像系统、扫描电子显微镜（scanning electron microscopy）、傅里叶变换红外光谱（Fourier-transform infrared spectroscopy）对合成的PSNPs进行了表征。经口摄入后，可在成年小鼠的大脑中检测到PSNPs。此外，一系列行为学分析结果显示，经口摄入PSNPs会引发记忆损伤。在大脑各类细胞中，PSNPs主要被小胶质细胞（microglia）摄取，且该摄取过程会诱发小胶质细胞激活。此外，从暴露于PSNPs的小胶质细胞中提取的条件培养基，会抑制海马神经元的活性。进一步的转录组分析（transcriptome analysis）结果显示，PSNPs可改变小胶质细胞的基因表达模式：神经炎症（neuroinflammation）水平显著升高，而神经营养因子（neurotrophic factors）的表达受到抑制。上述结果表明，PSNPs主要被小胶质细胞摄取，进而引发神经炎症反应增强，同时抑制神经营养因子的表达，这可能是导致认知损伤的原因。本研究结果阐明了纳米塑料对大脑的毒性作用机制与潜在危害，提示暴露于纳米塑料可能存在认知损伤风险。