Potentially toxic elements in the brains of people with multiple sclerosis

Abstract

Potentially toxic elements such as lead and aluminium have been proposed to play a role in the pathogenesis of multiple sclerosis (MS), since their neurotoxic mechanisms mimic many of the pathogenetic processes in MS. We therefore examined the distribution of several potentially toxic elements in the autopsied brains of people with and without MS, using two methods of elemental bio-imaging. Toxicants detected in the locus ceruleus were used as indicators of past exposures. Autometallography of paraffin sections from multiple brain regions of 21 MS patients and 109 controls detected inorganic mercury, silver, or bismuth in many locus ceruleus neurons of both groups, and in widespread blood vessels, oligodendrocytes, astrocytes, and neurons of four MS patients and one control. Laser ablation-inductively coupled plasma-mass spectrometry imaging of pons paraffin sections from all MS patients and 12 controls showed that combinations of iron, silver, lead, aluminium, mercury, nickel, and bismuth were present more often in the locus ceruleus of MS patients and were located predominantly in white matter tracts. Based on these results, we propose that metal toxicants in locus ceruleus neurons weaken the blood–brain barrier, enabling multiple interacting toxicants to pass through blood vessels and enter astrocytes and oligodendroglia, leading to demyelination.

The toxic metal hypothesis for neurological disorders

“…When sections from the brain of a man who died suddenly and unexpectedly were examined with autometallography, silver (confirmed on LA-ICP-MSI) was found in widespread brain regions (26). Cells containing most silver were locus ceruleus neurons, white (not grey) matter oligodendrocytes, blood vessel walls in the anterior pons and lateral geniculate nuclei (with less staining in microvessels in white matter elsewhere), white matter astrocytes, cerebellar dentate neurons, brain stem raphe neurons, ependymal cells, and neurons and glial cells adjacent to medium-sized venules in the leptomeninges, especially those deep in the lateral occipitotemporal gyrus of the inferomedial temporal lobe (Figure 4).…”

“…Not all CNS cells are involved in neurological disorders, and different toxic metals also affect only some types of cells in restricted regions of the nervous system (18,23,25,26,33,65). A site where many neurons contain toxic metals is the neuromelanin-containing locus ceruleus (22,149), though why only certain locus ceruleus neurons contain these metals, often adjacent to neurons without The other major region of the brain that harbors neuromelanincontaining neurons is the substantia nigra, whose neurons also bind and accumulate large amounts of toxic metals such as mercury and cadmium to form stable and insoluble complexes that remain inside the neurons for long periods of time (29,149).…”

“…This means that when looking for toxicants in human brains, large numbers of participants are required, since the relevant toxicant may only be observable if the toxicant exposure was recent or ongoing. An exception to this is the human locus ceruleus in the brain stem, which appears to selectively take up and retain metal toxicants for long periods of time (18)(19)(20)(21)(22)(23)(24)(25)(26). Therefore, examining the locus ceruleus can indicate previous exposures to toxicants that may have been cleared from other regions of the brain after permanently affecting cell function.…”

“…Another method is autometallography (AMG), a silver-based technique that can detect very small amounts of inorganic mercury, silver, and bismuth within cells (30, 31). AMG can be supplemented by laser ablation-inductively coupled-mass spectrometry imaging (LA-ICP-MSI) which can detect a large array of elements within cells and tissues, though at a lower resolution than autometallography (26). Using AMG and LA-ICP-MSI together gives a good picture of toxicant distribution within human brains.…”

Industrial impact on sustainable dairy farms: Essential elements, hazardous metals and polycyclic aromatic hydrocarbons in forage and cow's milk

“…Furthermore, owing to their chemical similarity, some HMs can displace essential elements (EEs) in organisms (i.e. sodium (Na), magnesium (Mg), potassium (K), and calcium (Ca)), causing neuronal diseases [ 14 ]. Organisms can metabolise PAHs to form more soluble hydroxylated derivatives, which are more reactive, bind proteins and DNA, and cause cancer [ 15 ].…”