p53/自噬通路在锰诱导的小胶质细胞活化中的作用

Manganese is an important environmental pollutant. Central nervous system is the most important target organ for manganese-induced toxicity. The exposure to manganese will lead to the symptoms similar to those of Parkinson's diseases. Microglia are immune cells in brain. The activation of microglia is an important characteristic of inflammatory progresses in central nervous system, which is involved in several nervous system diseases. Our former data have shown that the activation of microglia can be induced by manganese, but the mechanisms yet to be known. As a common tumor suppressor, in recent years, p53 has been found to be involved in the regulation of inflammatory reactions, including the activation of microglia. Autophagy is an important degradation pathway in eukaryotic cells, which plays important roles in keeping the intracellular homeostasis. Moreover, previous researches have shown that autophagy is also involved in the activation of microglia，and p53 has been found to regulate autophagy through different ways. In this study, both in vivo and in vitro models will be established. Immunohistochemistry, RT-PCR, Western blot, laser confocal scanning microscope, and other techniques will be performed to investigate the role of p53/autophagy pathway in manganese-induced microglial activation. We hope our results can provide new clues and theoretical foundations for the elucidation of manganese-induced neurotoxicity.

锰是一种重要的环境污染物，中枢神经系统是其毒性的重要靶器官，暴露后可引起类似帕金森病的临床表现。小胶质细胞是脑部的免疫细胞，其活化是中枢神经系统炎症反应的重要表现，与多种神经系统疾病的发生有关。我们此前已经发现锰可以诱导小胶质细胞活化，但是其机制尚不明确。p53是常见的肿瘤抑制因子，近年来发现p53参与了包括小胶质细胞活化在内的炎症调节。自噬是真核细胞中重要的降解途径，在维持细胞内环境稳态的过程中发挥重要的作用，有研究显示自噬同样与小胶质细胞活化有关。现有的证据表明p53可通过多种途径发挥对自噬的调控作用。本研究通过建立锰中毒动物模型和细胞模型的基础上，利用免疫组织化学、RT-PCR、Western blot、激光共聚焦显微镜等方法，探讨p53/自噬通路在锰诱导的小胶质细胞活化中的作用，从而为锰神经毒性的防护提供新的理论依据。