| 摘要: | 塑膠微粒(microplastics, MPs)為直徑小於5毫米的微型塑膠顆粒，是現今主要的環境汙染物，塑膠微粒會透過攝入或吸入的方式進入體內並堆積在組織或器官中，也會讓實驗小鼠肝臟、腎臟、腸胃道等器官產生發炎反應進而導致器官受損。先前實驗室研究發現，實驗小鼠利用管餵暴露在2μm聚苯乙烯塑膠微粒(polystyrene microplastics, PS-MPs)環境下連續8周，塑膠微粒會堆積在小鼠大腦海馬迴中，也會導致小鼠的學習與記憶力功能受損，但PS-MPs訊號如何影響大腦的機制及迴路仍然未知，本篇研究建立切除迷走神經的塑膠微粒小鼠模型以探討PS-MPs的訊號迴路。實驗過程中，在管餵小鼠2μm 0.016mg/g (body weight) PS-MPs 4周後進行迷走神經切除術，術後繼續管餵小鼠PS-MPs 4周，後續進行行為學相關實驗，由於迷走神經主要參與了大腦與腸胃之間的雙向溝通，結果顯示切除迷走神經的塑膠微粒小鼠在新穎事務識別測驗中較偏好探索新穎的積木，在水迷宮實驗中也記得逃生平台所在的位置，且花費較多時間待在逃生平台所放置的方位，顯示切除迷走神經後可以挽救PS-MPs對小鼠造成的學習與記憶力缺陷，間接證明PS-MPs是透過迷走神經迴路影響小鼠的學習與記憶力功能。由於塑膠微粒除了可以從消化道進入體內，還會透過呼吸進入肺臟中，因此本研究也建立吸入塑膠微粒小鼠模型，利用氣管餵藥讓小鼠吸入2μm 0.016mg/g (body weight) PS-MPs 8周或16周，後續進行行為學實驗檢測，結果顯示吸入16周PS-MPs小鼠在三室社交行為測驗的社交識別能力測試中塑膠微粒小鼠對於第二隻陌生小鼠的偏好指數有下降的趨勢，顯示吸入PS-MPs對於小鼠的社交識別能力產生些微的障礙，但PS-MPs對小鼠運動、焦慮、憂鬱、學習與記憶力方面皆沒有影響。總結本論文實驗結果，發現小鼠透過腸道暴露聚苯乙烯塑膠微粒所造成腦與神經行為的受損更甚於氣管暴露途徑。;Microplastics (MPs) are plastic pieces smaller than 5 mm that have emerged as one type of pollutant around the world. A grow bodying of evidence has shown that MPs accumulate in many organs, including the liver, kidney, and gut, causing inflammation and metabolic dysregulation in animal models. In our laboratory, we previously have demonstrated that polystyrene microplastics (PS-MPs) located in the hippocampus of brains of mice with 2 μm PS-MPs exposure through oral gavage for eight weeks. Those PS-MPs mice also showed learning and memory impairment. However, how PS-MPs change behavior in mice is still unknown. In this thesis, I fed mice with 2 μm 0.016 mg/g (body weight) PS-MPs through oral gavage for four weeks, and mice were performed vagotomy surgery afterward. Mice were continuously fed with PS-MPs through oral gavage for four weeks. In behavioral tests, ablation of the vagus nerve, the major nerve mediated gut and brain, rescued learning and memory of mice in novel object recognition and Morris water maze. Our study suggested that the adverse effects of PS-MPs in mice are in part via vagus nerve-dependent pathway. Since MPs exposure can be through ingestion and inhalation, I further investigated whether inhalation of PS-MPs causes brain damage and behavioral deficits. Mice were given PS-MPs through intratracheal administration for eight weeks and sixteen weeks followed by a battery of behavioral tests. The behavioral results showed that mice exposed to PS-MPs for sixteen weeks exhibited a trend toward a decrease in social novelty but not sociability in the three-chamber social interaction test. While learning and memory, locomotor activity, stress, and anxiety-like behaviors remained normal in PS-MPs mice compared to control mice. Taken together, the results indicate that exposure to PS-MPs in mice through oral gavage has more profound adverse effects on brain and behavior compared to mice exposed to PS-MPS via intratracheal administration. |
