塑膠微粒(MPs)定義為直徑小於5 mm的塑膠顆粒，是一種新興環境污染物。因為塑膠微粒體積較小，它們能夠經由食物鏈進入生物體內，並積聚在周圍組織/器官中，隨後對器官造成損害。本實驗室先前研究發現，聚苯乙烯塑膠微粒(PS-MPs)會影響公鼠學習與記憶能力，然而，PS-MPs如何影響大腦學習及記憶的分子機制仍然未知。本篇研究結果顯示，小鼠口服2μm PS-MPs八周後，利用拉曼光譜分析，可觀察到2 μm PS-MPs在肝臟及大腦海馬迴腦區中累積，而海馬迴是學習與記憶的重要腦區，進一步針對八周PS-MPs公鼠海馬迴進行分子分析後，發現對突觸可塑性和記憶力至關重要的Activity-regulated cytoskeleton-associated protein (Arc)，其mRNA和蛋白質表達在海馬迴中顯著降低，但在PS-MPs母鼠中則沒有明顯差異。由於Arc蛋白會影響α-氨基-3-羥基-5-甲基-4-異噁唑丙酸受體(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, AMPAR)亞基之一的突觸蛋白GluA1的內吞作用，因此發現GluA1在八周PS-MPs公鼠的海馬迴中異常增加。此外，本篇研究也發現暴露PS-MPs的公鼠八周後會會增加海馬迴促炎因子TNF-α與IL-1β的mRNA表現量及小膠質細胞的活化。綜合上述結果顯示小鼠暴露PS-MPs會改變突觸相關蛋白的表達以及神經發炎，進而削弱海馬迴依賴性學習和記憶。;Microplastics (MPs), defined as plastics particles less than 5 mm in diameter, are an emerging environmental pollutant in worldwide. Sine MPs are smaller in size, they can enter organisms via the food chain and accumulate in tissues/organs, subsequently causing damage to the organs. Previous study has confirmed that polystyrene micropartics (PS-MPs) can affect learning and memory ability in male mice. However, the molecular mechanism on how PS-MPs affecting learning and memory is still unknown. Using Raman spectroscopy analysis, 2 μm PS-MPs were found in the liver and the hippocampus of mice with oral administration of PS-MPs for eight weeks. Since the hippocampus is an important brain areafor learning and memory, Ifurther explored the molecular mechanism in the hippocampus. I found that the mRNA and protein expressions of activity-regulated cytoskeleton-associated protein (Arc), a key regulator for synaptic plasticity and learning and memory, was significantly decreased in the hippocampus, but there was no difference in PS-MPs female mice. The Arc protein can regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) endocytosis. I found that GluA1, a subunit of AMPAR, was aberrantly increased in the hippocampus of PS-MPs male mice.Moreover, I also found that exposure to PS-MPs in male mice for eight weeks increased the mRNA expression of pro-inflammatory cytokines TNF-α and IL-1β in the hippocampus and induced microglia activation. Taken together, these results suggest that exposure to PS-MPs in mice alters synapse-associated protein expression and neuroinflammation, thereby impairing hippocampal-dependent learning and memory.
