Age-Related Uptake of Heavy Metals in Human Spinal Interneurons

Toxic heavy metals have been implicated in the loss of spinal motoneurons in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Motoneuron loss in the spinal anterior horn is severe in ALS/MND at the time of death, making this tissue unsuitable for examination. We therefore examined spinal cords of people without muscle weakness to look for any presence of heavy metals that could make these neurons susceptible to damage. Spinal cord samples from 50 individuals aged 1-95 y who had no clinical or histopathological evidence of spinal motoneuron loss were studied. Seven mu m formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMG(HM)) which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or alpha-motoneurons based on their site and cell body diameter. Spinal interneurons containing heavy metals were present in 8 of 24 people (33%) aged 61-95 y, but not at younger ages. These AMG(HM) interneurons were most numerous in the lumbar spinal cord, with moderate numbers in the caudal cervical cord, few in the rostral cervical cord, and almost none in the thoracic cord. All people with AMG(HM) interneurons had occasional AMG(HM) staining in alpha-motoneurons as well. In one man AMG(HM) staining was present in addition in dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present in many spinal interneurons, and in a few alpha-motoneurons, in a large proportion of older people. Damage to inhibitory interneurons from toxic metals in later life could result in excitotoxic injury to motoneurons and may underlie motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis, sarcopenia and calf fasciculations.