帕金森病（Parkinson’s disease，PD）是一种好发于中老年的常见神经系统退行性疾病，临床表现包括运动障碍、嗅觉障碍、睡眠障碍、自主神经功能障碍及情绪障碍等。PD发病机制迄今尚不明确，可能与老龄化、环境和遗传因素密切相关。流行病学发现，暴露于环境毒物（如农药，有机溶剂，金属和其他污染物）能使PD患病风险增加。锰在脑内的蓄积能导致类似帕金森病的症状。最近有研究指出脑内锰的蓄积可能是PD的直接病因或加速PD进展的重要危险因素。本研究以慢性锰中毒PD小鼠为模型，拟探讨锰的神经毒性损伤的机制。前期工作中我们发现了囊泡谷氨酸转运体2（VGLUT2）在锰中毒小鼠中显著高表达。本研究拟从细胞和动物两个层面，通过构建重组慢病毒干预VGLUT2基因的表达或相关药物处理，探讨VGLUT2调控谷氨酸-谷氨酰胺循环在锰的神经毒性损伤的机制，为探索锰中毒及PD的发病机制提供了理论依据和新的治疗靶点。

Parkinson’s disease (PD) is a chronic, progressive, disabling neurodegenerative disorder that begins in mid to late life and is characterized by motor impairment, olfactory disturbances, sleep disorders, autonomic dysfunction and depression. The cause of PD is unknown, currently considered to be associated with aging, environment and genetic factors. Epidemiologic studies have found increased risk of PD associated with exposure to environmental toxicants such as pesticides, solvents, metals, and other pollutants. Excess accumulation of manganese (Mn) in the brain results in a neurological syndrome like PD. Recently, scientists have debated the possibility that Mn may have an etiological role in PD or that it may accelerate the expression of PD. In this study, we use the chronic Mn exposure mice to explore the pathogenesis of Mn neurotoxicity and found that VGLUT2 showed a dramatic increase in the Mn exposure mice. Recombinant retroviral vectors and drugs are constructed to regulate VGLUT2 levels both in vivo and in vitro, to investigate the mechanism of VGLUT2 regulated glutamate-glutamine cycle in the neurotoxicity of Mn. These findings will provide theoretical basis for the pathogenesis of Mn neurotoxicity and PD, give new insight into the treatment of these diseases.