Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA.
Neurotoxicology. 2018 Jan;64:50-59. doi: 10.1016/j.neuro.2017.06.011. Epub 2017 Jun 23.
Although an essential nutrient, manganese (Mn) can be toxic at high doses. There is, however, uncertainty regarding the effects of chronic low-level Mn-exposure. This review provides an overview of Mn-related brain and functional changes based on studies of a cohort of asymptomatic welders who had lower Mn-exposure than in most previous work. In welders with low-level Mn-exposure, we found: 1) Mn may accumulate in the brain in a non-linear fashion: MRI R1 (1/T1) signals significantly increased only after a critical level of exposure was reached (e.g., ≥300 welding hours in the past 90days prior to MRI). Moreover, R1 may be a more sensitive marker to capture short-term dynamic changes in Mn accumulation than the pallidal index [T1-weighted intensity ratio of the globus pallidus vs. frontal white matter], a traditional marker for Mn accumulation; 2) Chronic Mn-exposure may lead to microstructural changes as indicated by lower diffusion tensor fractional anisotropy values in the basal ganglia (BG), especially when welding years exceeded more than 30 years; 3) Mn-related subtle motor dysfunctions can be captured sensitively by synergy metrics (indices for movement stability), whereas traditional fine motor tasks failed to detect any significant differences; and 4) Iron (Fe) also may play a role in welding-related neurotoxicity, especially at low-level Mn-exposure, evidenced by higher R2* values (an estimate for brain Fe accumulation) in the BG. Moreover, higher R2* values were associated with lower phonemic fluency performance. These findings may guide future studies and the development of occupation- and public health-related polices involving Mn-exposure.
尽管锰（Mn）是一种必需的营养物质，但在高剂量下它可能是有毒的。然而，对于慢性低水平锰暴露的影响还存在不确定性。本综述基于对一组无症状焊工的队列研究，提供了与锰相关的大脑和功能变化的概述，这些焊工的锰暴露水平低于大多数先前的研究。在低水平锰暴露的焊工中，我们发现：1）Mn 可能以非线性方式在大脑中积累：只有在达到临界暴露水平（例如，过去 90 天内每天焊接超过 300 小时）后，MRI R1（1/T1）信号才会显著增加。此外，R1 可能比苍白球指数（苍白球的 T1 加权强度比与额叶白质）更敏感地捕捉 Mn 积累的短期动态变化，苍白球指数是 Mn 积累的传统标志物；2）慢性 Mn 暴露可能导致微观结构变化，基底节（BG）的扩散张量分数各向异性值较低，尤其是当焊接年限超过 30 年时；3）Mn 相关的微妙运动功能障碍可以通过协同度量（运动稳定性指数）敏感地捕捉到，而传统的精细运动任务未能检测到任何显著差异；4）铁（Fe）也可能在与焊接相关的神经毒性中发挥作用，尤其是在低水平 Mn 暴露时，BG 中的 R2值（大脑 Fe 积累的估计值）较高。此外，较高的 R2值与较低的语音流畅性表现相关。这些发现可能为未来涉及 Mn 暴露的研究和职业及公共卫生相关政策的制定提供指导。
