Mercury in human spinal motor neurons.

Inorganic mercury has been proposed as a neurotoxin that could cause sporadic motor neuron disease (SMND). We were therefore interested to see if mercury could be detected in the upper and lower motor neurons of SMND patients, and if mercury accumulated within motor neurons during life. Paraffin sections of formalin-fixed spinal cord (22 control adults, 20 SMND adults, 25 infants) and frontal primary motor cortex (9 control adults, 18 SMND adults, 20 infants) were stained with silver nitrate autometallography to detect ionic mercury. Mercury was found in the spinal motor neurons of 36% of adult control cases and 45% of adult SMND cases, with no significant difference between groups. No mercury was seen in infant spinal motor neurons, or in any adult or infant corticomotoneurons. In conclusion, many humans appear to accumulate mercury in their spinal motor neurons by the time they are adults, but mercury does not appear to play a major role in the loss of upper or lower motor neurons in SMND.

Gender differences in the uptake of inorganic mercury by motor neurons.

Gender differences have been noted in the tissue distribution of mercury. We sought to determine if the uptake of low-dose inorganic mercury into motor neurons differs between male and female mice. Four male and four female mice were injected i.p. with 0.5 mg HgCl2/kg. In 50-microns sections of lumbar spinal cord stained with autometallography, six motor neuron cell bodies were selected for study. The volume percentage of mercury granules in the cell bodies was estimated using a confocal microscope. Mercury granules occupied more perikaryal volume in motor neurons from female mice (mean 3.7%) than from male mice (mean 2.2%) (p < or = 0.05). After the same dose, the amount of renal mercury measured by mass spectrometry was significantly less in six female than five male mice. In conclusion, female mice take up more inorganic mercury into their motor neurons than do male mice. This may be related to a smaller deposition of mercury in the female kidney, leaving more circulating mercury available to be taken up by motor axons.

Uptake of inorganic mercury by the human brain.

A 24-year-old man injected himself intravenously with metallic mercury in a suicide attempt, and died 5 months later after cutting his wrists. The brain was removed at postmortem and 7-micron paraffin sections were cut from representative blocks. Dense deposits of mercury were found on autometallography in large cortical motor neurons, but in no other cerebral neurons. Smaller mercury deposits were found in the brain stem (in the mesencephalic trigeminal nucleus, noradrenergic neurons, and in neurons for extraocular muscles), the cerebellum (in the dentate nucleus) and in lateral motor neurons in the C2/3 spinal cord. Mercury deposits were found in glial cells in all regions. The finding that elemental mercury enters human cortical motor neurons in preference to other cerebral neurons raises the possibility that this neurotoxin may play a part in the pathogenesis of some human motor neuron diseases.

Motor neuron uptake of low dose inorganic mercury.

In animals, inorganic mercury can bypass the blood brain barrier and enter motor neurons. We sought to determine the lowest injected dose of mercury that could be detected in mouse motor neurons. Mice were injected intraperitoneally with mercuric chloride in doses from 0.05 to 2 micrograms/g body weight and studied between 5 days and 18 months after injection. After formalin fixation, 7 microns sections of cerebrum, cerebellum, brain stem, spinal cord and kidney were stained with silver nitrate autometallography. Five days after injection, mercury granules were detected at doses from 0.2 microgram/g upwards in the cell bodies of spinal and brain stem motor neurons, more granules being seen at the higher doses. Mercury granules were also seen in 5% of posterior root ganglion neurons. At doses from 0.05 microgram/g upwards mercury was detected 5 days later in renal tubule cells. Mercury was still present in motor neurons 6-11 months after injection, but by this time mercury had been cleared from the kidneys. Low doses of inorganic mercury are therefore selectively taken up and retained by motor neurons, making this neurotoxin a good candidate for a cause of sporadic motor neuron disease.