锰对认知功能的影响及其分子作用机制研究

项目名称： 锰对认知功能的影响及其分子作用机制研究

项目编号： No.21467003

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 邹云锋

作者单位： 广西医科大学

项目金额： 53万元

中文摘要： 慢性锰暴露可致机体认知能力下降，但是其分子毒理机制仍不清楚。最近我们的人群调查及动物实验揭示了锰暴露可能通过降低脑源性神经因子(BDNF)的含量，从而使机体的认知能力降低。但其他一些已证明与认知功能有关的基因是否在锰导致机体认知功能损害中发挥了作用？目前少有报道。本研究采用动物实验和人群流行病学调查相结合的方法：用Morris水迷宫试验、荧光定量PCR、western-blot等来验证SPON1、APP、APOE等基因是否和锰暴露导致认知功能下降有关，将关联分析有意义的基因敲除后的小鼠染锰并验证该基因在锰对认知功能影响中的作用机制。最后在锰慢性暴露的人群中，采用蒙特利尔认知评估量表（MoCA）和神经行为核心测试组合（WHO-NCTB）来评估其认知功能，并检测锰内外暴露的剂量及血浆中锰含量。有望通过该研究进一步阐明锰导致机体认知功能下降的作用机制并找到新的锰暴露的早期效应生物标志物。

中文关键词： 锰；认知功能；分子机制

英文摘要： Chronic exposure to manganese can lead to decrease of cognitive function, but the molecular toxicological mechanism is still unclear. Recently, our population studies and animal experiments revealed that manganese exposure may impair cognitive function by decreasing the brain-derived neurotrophic factor (BDNF) levels. However, there are few reports if cognition related genes which were demonstrated play a role in the impairment of cognitive abilities induced by manganese. This study combines animal experiments and population epidemiological investigations, such as Morris water maze test, Quantitative PCR and western-blot to verify SPON1、APP、APOE whether are associated with cognitive deficits induced by manganese, and then select some genes which are related to cognition to study the effects of these genes on this mechanism in knockout and manganese exposure mice. At last, we use the Montreal Cognitive Assessment (MoCA) and Neurobehavioral Core Test Battery(NCTB) to evaluate cognitive function, and detect manganese exposure dose in vivo and vitro and plasma cognition among population of long-term chronic exposure to manganese. We hope that we can explain the mechanism further and find new early biomarkers of manganese exposure through this study.

英文关键词： manganese;Cognitive function;Molecular mechanism