School of Health Sciences, Purdue University, West Lafayette, IN, USA; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
School of Health Sciences, Purdue University, West Lafayette, IN, USA.
Neurotoxicology. 2018 Jan;64:30-42. doi: 10.1016/j.neuro.2017.08.013. Epub 2017 Sep 2.
Excessive occupational exposure to Manganese (Mn) has been associated with clinical symptoms resembling idiopathic Parkinson's disease (IPD), impairing cognitive and motor functions. Several studies point towards an involvement of the brain neurotransmitter system in Mn intoxication, which is hypothesized to be disturbed prior to onset of symptoms. Edited Magnetic Resonance Spectroscopy (MRS) offers the unique possibility to measure γ-amminobutyric acid (GABA) and other neurometabolites in vivo non-invasively in workers exposed to Mn. In addition, the property of Mn as Magnetic Resonance Imaging (MRI) contrast agent may be used to study Mn deposition in the human brain. In this study, using MRI, MRS, personal air sampling at the working place, work history questionnaires, and neurological assessment (UPDRS-III), the effects of chronic Mn exposure on the thalamic GABAergic system was studied in a group of welders (N=39) with exposure to Mn fumes in a typical occupational setting. Two subgroups of welders with different exposure levels (Low: N=26; mean air Mn=0.13±0.1mg/m; High: N=13; mean air Mn=0.23±0.18mg/m), as well as unexposed control workers (N=22, mean air Mn=0.002±0.001mg/m) were recruited. The group of welders with higher exposure showed a significant increase of thalamic GABA levels by 45% (p<0.01, F(1,33)=9.55), as well as significantly worse performance in general motor function (p<0.01, F(1,33)=11.35). However, welders with lower exposure did not differ from the controls in GABA levels or motor performance. Further, in welders the thalamic GABA levels were best predicted by past-12-months exposure levels and were influenced by the Mn deposition in the substantia nigra and globus pallidus. Importantly, both thalamic GABA levels and motor function displayed a non-linear pattern of response to Mn exposure, suggesting a threshold effect.
职业性锰暴露过度与类似特发性帕金森病（IPD）的临床症状有关，会损害认知和运动功能。多项研究表明，脑神经递质系统参与了锰中毒，锰中毒在症状出现前就可能被扰乱。经编辑的磁共振波谱（MRS）提供了一种独特的可能性，可以无创地在接触锰的工人体内测量γ-氨基丁酸（GABA）和其他神经代谢物。此外，锰作为磁共振成像（MRI）造影剂的特性可用于研究人类大脑中的锰沉积。在这项研究中，使用 MRI、MRS、工作场所的个人空气采样、工作史问卷和神经学评估（UPDRS-III），在一组在典型职业环境中接触锰烟尘的焊工（N=39）中研究了慢性锰暴露对丘脑 GABA 能系统的影响。根据接触水平的不同，招募了两组焊工（低暴露组：N=26；平均空气 Mn=0.13±0.1mg/m；高暴露组：N=13；平均空气 Mn=0.23±0.18mg/m），以及未暴露的对照组工人（N=22；平均空气 Mn=0.002±0.001mg/m）。高暴露组的丘脑 GABA 水平显著增加了 45%（p<0.01，F（1，33）=9.55），且一般运动功能明显下降（p<0.01，F（1，33）=11.35）。然而，低暴露组的焊工在 GABA 水平或运动表现方面与对照组没有差异。此外，在焊工中，丘脑 GABA 水平与过去 12 个月的暴露水平密切相关，且受黑质和苍白球中锰沉积的影响。重要的是，丘脑 GABA 水平和运动功能对锰暴露的反应呈非线性模式，提示存在阈值效应。
