INCREASED INORGANIC MERCURY IN SPINAL MOTOR-NEURONS FOLLOWING CHELATING-AGENTS

Heavy meta I toxicity has been implicated in the pathogenesis of motor neuron diseases. In an attempt to assess the efficacy of chelating ag ents to remove mercury from motor neurons, we quantitated the effect o f the chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3 -dimercaptopropane-1-sulphonate (DMPS) on the burden of inorganic merc ury in mouse spinal motor neurons. Mice were injected intraperitoneall y with 1.0 mg HgCl2/kg body weight and one week later with either 4,40 0 mg/kg DMPS, 3,600 mg/kg DMSA or 5% NaHCO3 (control) over 4 weeks. Me rcury deposits in motor neurons of 50 mu m frozen sections of lumbar s pinal cord were visualised with an autometallographic technique. Optic al sections of silver-enhanced deposits were acquired using a confocal microscope in reflective mode and the volume of the deposits within t he perikaryon was estimated. Mercury deposits occupied significantly m ore volume in motor neurons after both DMPS (7.4%, SD +/- 0.7%) and DM SA (8.0% +/- SD 0.7%) treatment than in controls (4.3%, SD +/- 1.7%). The higher levels of neuronal inorganic mercury may be due to increase d entry of mercury into motor axons across the neuromuscular function as a result of chelator-induced elevated circulating mercury. (C) 1996 Intox Press.