Abstract

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 μm formalin-fixed paraffin-embedded sections were stained for heavy metals with silver nitrate autometallography (AMGHM) which detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were classified as interneurons or α-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 AMGHM 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 AMGHM interneurons had occasional AMGHM staining in α-motoneurons as well. In one man AMGHM 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 α-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.

Highlights

  • The cause of the motoneuron loss that occurs in the neurodegenerative disorder amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) remains largely unknown [1]

  • In an attempt to overcome these problems we examined the spinal cords of people who had no evidence of motoneuron damage, to see if any groups of neurons took up toxicants that could cause later motoneuron dysfunction

  • Three individuals with autometallography-demonstrable heavy metals (AMGHM) interneurons had a history of multiple sclerosis and one each had had dementia, Parkinson’s disease, bipolar disorder, arthritis, and no previous illness

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Summary

Introduction

The cause of the motoneuron loss that occurs in the neurodegenerative disorder amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) remains largely unknown [1]. Possibilities include environmental, genetic, or epigenetic factors, or combinations of these, but so far no common cause for the sporadic form of the disease has emerged [2]. The genetic or environmental causes of other age-related losses or dysfunctions of motoneurons that occur in normal aging [3,4], the muscle wasting of sarcopenia that occurs in later life [5], or benign fasciculation syndromes [6] are still not identified. Heavy Metals in Human Spinal Interneurons data collection and analysis, decision to publish, or preparation of the manuscript

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