Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Basic Clin Pharmacol Toxicol. 2012 Aug;111(2):126-32. doi: 10.1111/j.1742-7843.2012.00872.x. Epub 2012 Mar 17.
Amyotrophic lateral sclerosis (ALS) affects anterior horn cells of the spinal cord causing an indolent slow and steady deterioration of muscle strength leading inevitably to death in respiratory failure. ALS is a model condition for neurodegenerative disorders. Exposure to different agents dispersed in the environment has been suggested to cause neurodegeneration but no convincing evidence for such a link has yet been presented. Respiratory exposure to metallic mercury (Hg(0)) from different sources may be suspected. Body distribution of metallic mercury is fast and depends on solubility properties. Routes of transport, metabolism, excretion and biological half-life determine the overall toxic effects. Inhalation experiments were performed in 1984 where small marmoset monkeys (Callithrix jacchus) were exposed to (203) Hg(0 vapour) mixed into the breathing air (4-5 μg/l). After 1 hr of exposure, they were killed and whole body autoradiograms prepared to study the distribution of mercury within organs. Autoradiograms showed that Hg was deposited inside the spinal cord. Areas of enhanced accumulation anatomically corresponding to motor nuclei could be observed. This study describes a reinvestigation, with new emphasis on the spinal cord, of these classical metal exposure data in a primate, focusing on their relevance for the causation of neurodegenerative disorders. A comparison with more recent rodent experiments with similar findings is included. The hypothesis that long-time low-dose respiratory exposure to metals, for example, Hg, contributes to neurodegenerative disorders is forwarded and discussed.
肌萎缩侧索硬化症(ALS)影响脊髓前角细胞,导致肌肉力量缓慢而稳定地恶化,最终不可避免地导致呼吸衰竭死亡。ALS 是神经退行性疾病的典型病症。环境中分散的不同物质的暴露被认为会导致神经退行性变,但目前还没有令人信服的证据证明这种联系。呼吸暴露于不同来源的金属汞(Hg(0))可能会受到怀疑。金属汞的体内分布速度很快,取决于其溶解度特性。运输途径、代谢、排泄和生物半衰期决定了整体毒性效应。1984 年进行了吸入实验,其中小绢毛猴(Callithrix jacchus)暴露于(203)Hg(0)蒸气混合在呼吸空气中(4-5μg/l)。暴露 1 小时后,将它们杀死并制备全身放射自显影图,以研究汞在器官内的分布。放射自显影显示汞沉积在脊髓内。可以观察到与运动核在解剖学上相对应的汞积累区域增强。本研究重新调查了这些在灵长类动物中具有经典金属暴露数据的研究,重点关注它们与神经退行性疾病的因果关系,同时强调了新的重点是脊髓。包括与具有类似发现的最近啮齿动物实验的比较。提出并讨论了长期低剂量呼吸暴露于金属(例如 Hg)会导致神经退行性疾病的假设。