The Stacey Motor Neuron Disease Laboratory, Department of Pathology (Neuropathology), The University of Sydney, Australia.
Toxicol Lett. 2011 Feb 25;201(1):58-61. doi: 10.1016/j.toxlet.2010.12.005. Epub 2010 Dec 15.
Heavy metals have long been suspected to be involved in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS), but evidence for their toxic effects on motor neurons is limited. Characteristic mislocalisation of TDP-43 is seen in the motor neurons of patients with SALS, resulting in a lack of nuclear staining and cytoplasmic inclusions. To find out if a heavy metal can cause these TDP-43 changes, mice were exposed to varying doses of mercuric chloride or mercury vapor. Sections of spinal cord were then immunostained with phosphorylation-dependent and independent TDP-43 antibodies. All mercury-exposed mice had mercury granules in their motor neurons, even up to 2 years after exposure. However, the pathognomic changes in TDP-43 that are seen in SALS were not present in the motor neurons of these mice. The results do not therefore support a hypothesis of inorganic mercury-induced damage to motor neurons leading to SALS. This experimental model could be further used to test which of the environmental toxicants implicated in SALS may in fact cause the disease.
重金属长期以来一直被怀疑与散发性肌萎缩侧索硬化症（SALS）的发病机制有关，但它们对运动神经元的毒性作用的证据有限。在 SALS 患者的运动神经元中可以看到 TDP-43 的特征性定位异常，导致核染色缺失和细胞质包涵体。为了确定重金属是否会导致这些 TDP-43 变化，研究人员将小鼠暴露于不同剂量的氯化汞或汞蒸气中。然后用磷酸化依赖和不依赖的 TDP-43 抗体对脊髓切片进行免疫染色。所有暴露于汞的小鼠的运动神经元中都有汞颗粒，甚至在暴露 2 年后仍有。然而，在这些小鼠的运动神经元中并未出现 SALS 中所见的 TDP-43 的特征性变化。因此，该结果并不支持无机汞引起运动神经元损伤导致 SALS 的假说。该实验模型可进一步用于测试在 SALS 中涉及的环境毒物中哪些实际上可能导致该疾病。
