Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human primates
Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human primates
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DOI：
10.1016/j.expneurol.2006.06.015
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发表时间：
2006-12-01
影响因子：
5.3
通讯作者：
Schneider, Jay S.
中科院分区：
文献类型：
--
作者：
Guilarte, Tomas R.;Chen, Ming-Kai;Schneider, Jay S.
我们测试的假设，慢性锰（Mn）暴露引起的运动异常介导的非人灵长类动物纹状体的黑质纹状体多巴胺系统的功能障碍。在长期暴露于Mn和正电子发射断层扫描（PET）研究的同时，监测动物的运动功能和一般活动，研究纹状体中的体内多巴胺释放、多巴胺转运蛋白和多巴胺受体。获得全血和脑中金属浓度的分析，并使用死后脑组织分析来确认体内PET结果。慢性锰暴露导致微妙的运动功能缺陷，这与在纹状体中多巴胺（DA）末端完整性或多巴胺受体标记物的变化的情况下体内多巴胺释放的显著减少有关。黑质纹状体DA系统功能的这些改变，观察到在人类的环境，医疗和职业暴露的上限范围内的血液锰浓度。这些研究结果表明，锰暴露的非人灵长类动物表现出微妙的运动功能缺陷有一个明显完整的，但功能失调的黑质纹状体DA系统，并提供了一个新的机制锰对多巴胺能系统的影响。(c)2006年爱思唯尔公司All rights reserved.
We tested the hypothesis that movement abnormalities induced by chronic manganese (Mn) exposure are mediated by dysfunction of the nigrostriatal dopamine system in the non-human primate striatum. Motor function and general activity of animals was monitored in parallel with chronic exposure to Mn and Positron Emission Tomography (PET) studies of in vivo dopamine release, dopamine transporters and dopamine receptors in the striaturn. Analysis of metal concentrations in whole blood and brain was obtained and post-mortem, analysis of brain tissue was used to confirm the in vivo PET findings. Chronic Mn exposure resulted in subtle motor function deficits that were associated with a marked decrease of in vivo dopamine release in the absence of a change in markers of dopamine (DA) terminal integrity or dopamine receptors in the striaturn. These alterations in nigrostriatal DA system function were observed at blood Mn concentrations within the upper range of environmental, medical and occupational exposures in humans. These findings show that Mn-exposed non-human primates that exhibit subtle motor function deficits have an apparently intact but dysfunctional nigrostriatal DA system and provide a novel mechanism of Mn effects on the dopaminergic system. (c) 2006 Elsevier Inc. All rights reserved.