Possible involvement of environmental selenium in the etiology of amyotrophic lateral sclerosis

The metalloid selenium (Se) is of considerable interest in environmental health, since it has both toxicological and nutritional properties, though these potential effects are still debated and not entirely elucidated. The safe range of Se intake in the human has not been clearly defined, but it appears to be very narrow, as also confirmed by recent epidemiologic and laboratory studies. Moreover, it is well recognized that the different Se compounds have distinctive biological activities, and the inorganic species appear to be the most toxic ones, despite being retained in the body to a much lesser extent than the organic forms.Two epidemiologic investigations carried out in South Dakota and in northern Italy have suggested that environmental Se species, particularly the inorganic ones, might be involved in the etiology of a severe motor neuron disease of unknown origin, sporadic amyotrophic lateral sclerosis (ALS). Veterinary medicine observations and toxicological studies have shown that some Se compounds have, in swine and in cattle, a selective toxicity to motor neurons, thus strengthening the still limited epidemiologic evidence. Furthermore, neurotoxic effects of Se species have been shown in several laboratory studies and even at very low concentrations, particularly for the inorganic species. Following Se treatment, a decrease in locomotor activity in rats, hind limb paralysis and cardiorespiratory effects in mice, and paralysis in an experimental worm model have been observed. In laboratory studies carried out using inorganic and less frequently organic Se forms in different animal species, the metalloid has been shown to interfere with several pathogenetic mechanisms potentially related to neurotoxicity, such as inhibition of prostaglandin D synthase in the brain, inhibition of squalene monooxigenase with potential cholesterol synthesis abnormalities, peripheral segmental demelination, and paralysis, increase in dopamine and its metabolies, inhibition of succinic dehydrogenase, acetylcholine esterase and Na+/K+ ATPase, and induction of seizures. Se has also been shown to induce toxic effects in rabbit vascular muscle, in rat heart muscle and in chick muscle, and in addition to inhibit axonal conduction and excitatory postsynaptic potentials, indicating the capacity of this metalloid to alter both nervous and muscle functions.Overall, these findings from the epidemiologic and the toxicological literature indicate that environmental Se, particularly when occurring in its inorganic forms in drinking waters or occupational settings, might be a risk factor for ALS, suggesting the opportunity to further investigate this issue.