Atrophy of large myelinated motor axons and declining muscle grip strength following mercury vapor inhalation in mice.

The effects of acute mercury vapor (Hg(0)) exposure on the peripheral motor system have not been previously addressed in the literature. Early case studies report that acute exposure in humans can cause symptoms resembling motor neuron disease (MND). Mercury granules can be histochemically demonstrated in the cytoplasm of murine motor neurons following Hg(0) exposure, suggesting it is transported from the neuromuscular junction (NMJ) to the cell body by retrograde axonal transport mechanisms. We considered the hypothesis that morphological damage to the peripheral motor axonal cytoskeleton possibly involving neurofilaments (NFs) follows Hg(0) exposure. Eight-week-old wild type (Wt) 129S/v mice were exposed to 500 microg/m(3) of Hg(0) for 4 h in an experimental vapor exposure chamber. Forelimb grip strength (FGS) was measured over 4-wk intervals prior to removal of the murine phrenic nerves (MPN) 7 mo postexposure. Autometallography of 7-microm-thick spinal-cord sections from Hg(0)-exposed mice confirmed the presence of mercury deposits in ventral horn motor neurons. The morphology of the myelinated motor axons was assessed by computer-assisted image analysis of 1-microm-thick resin cross sections of the MPN. The group exposed to Hg(0) showed a significant reduction in the mean axon caliber, p < .0001. Gaussian spectral analysis of axon diameter distribution showed atrophy principally to large myelinated fibers, a subpopulation of axons that is also affected in MND. This atrophic change was also accompanied by an increased irregularity in axon shape. FGS initially increased with age until 20 wk and then progressively decreased after 22 wk to 36 wk. In conclusion, Hg(0) exposure appears to reduce axon diameter, suggesting axon caliber-determining cytoskeletal components such as neurofilaments may be damaged by heavy metal-induced oxidative stress mechanisms, resulting in functional changes to motor units.