Inorganic mercury in human astrocytes, oligodendrocytes, corticomotoneurons and the locus ceruleus: implications for multiple sclerosis, neurodegenerative disorders and gliomas

Pamphlett, Roger; Jew, Stephen Kum

doi:10.1007/s10534-018-0124-4

Cited by 45 publications

(37 citation statements)

References 61 publications

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“…Our findings of mercury adjacent to the nuclei of oligodendrocytes recapitulates findings in the cerebral cortex from this man who injected himself with metallic mercury [40], as well as ultrastructural studies of rats exposed to mercury which showed mercury binding to oligodendrocyte nuclear membranes [34] and lysosomes [36]. Mercury in oligodendrocytes could affect myelin metabolism and axonal conductance, which has the potential to slow nerve impulses from the geniculate nuclei to their respective primary cortices.…”

Section: Plos Onesupporting

confidence: 84%

Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei

et al. 2020

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Interference with the transmission of sensory signals along visual and auditory pathways has been implicated in the pathogenesis of hallucinations. The relay centres for vision (the lateral geniculate nucleus) and hearing (the medial geniculate nucleus) appear to be susceptible to the uptake of circulating mercury. We therefore investigated the distribution of mercury in cells of both these geniculate nuclei. Materials and methods Paraffin-embedded tissue sections containing the lateral geniculate nucleus were obtained from 50 adults (age range 20-104 years) who at autopsy had a variety of clinicopathological conditions, including neurological and psychiatric disorders. The medial geniculate nucleus was present in seven sections. Sections were stained for mercury using autometallography. Laser ablation-inductively coupled plasma-mass spectrometry was used to confirm the presence of mercury. Results Ten people had mercury in cells of the lateral geniculate nucleus, and in the medial geniculate nucleus of three of these. Medical diagnoses in these individuals were: none (3), Parkinson disease (3), and one each of depression, bipolar disorder, multiple sclerosis, and mercury self-injection. Mercury was distributed in different groups of geniculate capillary endothelial cells, neurons, oligodendrocytes, and astrocytes. Mass spectrometry confirmed the presence of mercury. Conclusion Mercury is present in different combinations of cell types in the lateral and medial geniculate nuclei in a proportion of people from varied backgrounds. This raises the possibility that mercury-induced impairment of the function of the geniculate nuclei could play a part in the

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Section: Plos Onesupporting

confidence: 84%

Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei

et al. 2020

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“…Because AD patients display altered metal dyshomeostasis [64] that manifests in different ways, including altered plasma/CSF (cerebrospinal fluid) ratios for various metal ions including Hg(II), it has been suggested that AD pathology may involve a compromised blood-CSF barrier [93,137]. On the other hand, the brain metal chemistry is notoriously complex, and studies on beluga whales and humans indicate that Hg(II) and other metal ions accumulate into different brain regions also for non-AD individuals [138][139][140]. One study with a limited number of patients reported elevated Hg concentrations in the two brain regions nucleus basalis of Meynert (NBM) and amygdala [135].…”

Section: Mercury and Ad: Clinical Studies And Sources Of Exposurementioning

confidence: 99%

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

et al. 2019

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Brains and blood of Alzheimer’s disease (AD) patients have shown elevated mercury concentrations, but potential involvement of mercury exposure in AD pathogenesis has not been studied at the molecular level. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. Aβ peptide fibrillization is known to be modulated by metal ions such as Cu(II) and Zn(II). Here, we study in vitro the interactions between Aβ peptides and Hg(II) ions by multiple biophysical techniques. Fluorescence spectroscopy and atomic force microscopy (AFM) show that Hg(II) ions have a concentration-dependent inhibiting effect on Aβ fibrillization: at a 1:1 Aβ·Hg(II) ratio only non-fibrillar Aβ aggregates are formed. NMR spectroscopy shows that Hg(II) ions interact with the N-terminal region of Aβ(1–40) with a micromolar affinity, likely via a binding mode similar to that for Cu(II) and Zn(II) ions, i.e., mainly via the histidine residues His6, His13, and His14. Thus, together with Cu(II), Fe(II), Mn(II), Pb(IV), and Zn(II) ions, Hg(II) belongs to a family of metal ions that display residue-specific binding interactions with Aβ peptides and modulate their aggregation processes.

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“…Astrocytes has been postulated in a primary role of MS [22]. Recently, inorganic mercury was found in astrocytes from autopsy-obtained tissue from a man who injected himself intravenously with metallic mercury [23]. This provides the direct evidence that mercury could play a role in the pathogenesis of MS.…”

Section: Discussionmentioning

confidence: 91%

Dental Amalgam Fillings and Multiple Sclerosis: A Nationwide Population-Based Case–Control Study in Taiwan

Tseng

Chen

et al. 2020

IJERPH

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Multiple sclerosis (MS) is an inflammatory neurological disease characterized by autoimmune-mediated demyelination of the central nervous system. Genetic and environmental factors may contribute to the development of MS. This has not been confirmed yet. Dental amalgam has long been controversial in MS due to its mercury content but the toxicological implications of mercury-containing amalgam fillings (AMF) for MS remain to be elucidated. We conducted a case–control study to investigate the association between AMF and the risk of MS from the Taiwanese National Health Insurance Research Database (NHIRD). Case (n = 612) and control (n = 612) groups were matched by sex, age, urbanization level, monthly income, and Charlson comorbidity index by propensity score matched with a 1:1 ratio from 2000 to 2013. Differences between cases and controls was not statistically significant (OR: 0.82, 95% CI = 0.65–1.05). In subjects stratified by gender, MS was also not associated with AMF for women (OR: 0.743, 95% CI = 0.552–1.000) and men (OR: 1.006, 95% CI = 0.670–1.509), respectively. In summary, this Taiwanese nationwide population-based case–control study did not find an association between MS and AMF.

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Inorganic mercury in human astrocytes, oligodendrocytes, corticomotoneurons and the locus ceruleus: implications for multiple sclerosis, neurodegenerative disorders and gliomas

Cited by 45 publications

References 61 publications

Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei

Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

Dental Amalgam Fillings and Multiple Sclerosis: A Nationwide Population-Based Case–Control Study in Taiwan

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