Inorganic mercury within motor neurons does not cause the TDP-43 changes seen in sporadic ALS.

ABSTRACT

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.