4.5 Article

Principal Component Analysis of Striatal and Extrastriatal D2 Dopamine Receptor Positron Emission Tomography in Manganese-Exposed Workers

期刊

TOXICOLOGICAL SCIENCES
卷 182, 期 1, 页码 132-141

出版社

OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfab045

关键词

manganese; PET; D2 receptors; PCA

资金

  1. National Institutes of Health [R01ES021488, K23ES021444, K24ES017765, K01ES028295, R01ES013743, R01ES021488-02S1, P42ES004696, ICTS UL1RR024992]
  2. American Parkinson Disease Association (APDA)
  3. Advanced Research Center at Washington University
  4. Greater St. Louis Chapter of the APDA

向作者/读者索取更多资源

The study utilized positron emission tomography to investigate the relationship between manganese exposure, D2 dopamine receptors, and motor function, finding associations between manganese exposure and D2 receptor binding in both striatal and extrastriatal regions. Multifocal alterations in D2 receptor expression were linked to motor dysfunction.
The relationships between the neurotoxicant manganese (Mn), dopaminergic pathology, and parkinsonism remain unclear. Therefore, we used [C-11] (N-methyl)benperidol (NMB) positron emission tomography to investigate the associations between Mn exposure, striatal and extrastriatal D2 dopamine receptors (D2R), and motor function in 54 workers with a range of Mn exposure. Cumulative Mn exposure was estimated from work histories, and all workers were examined by a movement specialist and completed a Grooved Pegboard test (GPT). NMB D2R nondisplaceable binding potentials (BPND) were calculated for brain regions of interest. We identified 2 principal components (PCs) in a PC analysis which explained 66.8% of the regional NMB BPND variance (PC1 = 55.4%; PC2 = 11.4%). PC1 was positively correlated with NMB binding in all regions and inversely correlated with age. PC2 was driven by NMB binding in 7 brain regions (all p < .05), positively in the substantia nigra, thalamus, amygdala, and medial orbital frontal gyrus and negatively in the nucleus accumbens, anterior putamen, and caudate. PC2 was associated with both Mn exposure status and exposure duration (years). In addition, PC2 was associated with higher Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores and slower GPT performance. We conclude Mn exposure is associated with both striatal and extrastriatal D2R binding. Multifocal alterations in D2R expression are also associated with motor dysfunction as measured by both the GPT and UPDRS3, demonstrating a link between Mn exposure, striatal and extrastriatal D2R expression, and clinical neurotoxicity.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据