锰（Mn）既是环境中比较常见的重金属污染物，又是帕金森病的环境致病因素之一。以往关于锰神经毒性的研究，多集中在氧化损伤和影响神经递质代谢方面。但是，锰是如何干扰突触囊泡转运和神经递质释放的具体机制研究却未见报道。本项目拟在申请人既往对神经细胞内谷氨酸代谢和α-突触核蛋白（α-syn）的研究基础上，进一步提出推断：在锰中毒的早期，首先α-syn蛋白表达异常并出现寡聚化，过多的α-syn蛋白通过与Rab3a蛋白的相互作用，干扰了突触囊泡中神经递质的转运及释放，进而导致突触间隙神经递质的异常变化。本项目将利用微透析与高效液相色谱相结合的技术，动态监测神经突触间隙氨基酸类神经递质的变化；并结合蛋白芯片技术，验证锰通过对突触囊泡相关蛋白的影响，干扰神经递质的释放。此项目不仅为预防和治疗锰中毒及其他神经退行性疾病提供一定的实验和理论依据，而且在加强锰中毒早期防治和保护锰接触者健康方面有重要的现实意义。

Manganese (Mn) is one of the common heavy metal pollutants in the environment and one of the environmental pathogenic factors of Parkinson's disease. Previous studies on the mechanism of Mn neurotoxicity, more concentrated in the oxidative damage and disturbing neurotransmitter metabolism. However, it has not been reported that Mn is how to interfere with synaptic vesicle trafficking and neurotransmitter release. This project aims to, based on the research on the neuronal glutamate metabolism and alpha-synuclein (α -syn) in the past, further put forward inference: In the early of Mn poisoning, first α-syn protein abnormal expression and the emergence of oligomerization, excessive α-syn protein by interacting with Rab3a protein, interfere with the transport and release of neurotransmitter in the synaptic vesicles, which led to the abnormal changes of neurotransmitters in synaptic gap. This project will use microdialysis combined with high performance liquid chromatography (HPLC) technology, dynamic monitoring the change of amino acids neurotransmitters in neural synaptic gap; and use the protein chip technology, validation of manganese disturbing the neurotransmitter release by influence on protein in synaptic vesicles. This project will not only provide some experimental and theoretical basis for the prevention and treatment of manganese poisoning and other neurodegenerative diseases, but also has important practical significance in strengthening manganese poisoning early health prevention.