Neurotoxicity of ß-HgS differs from environmental mercury pollutants (MeHgCl and HgCl2) in Neuro-2a cell.

ß-HgS, differing from environmental mercury pollutants (MeHgCl and HgCl2) in chemical form, is used as traditional medicine in Asian countries for thousands of years. In this study, Neuro-2a cells were exposed to ß-HgS, MeHgCl and HgCl2 (5 µM) for 6-24 h. The cell viability of ß-HgS was higher than MeHgCl with 25.9% and 72.4% in 12 h and 24 h respectively. As the incubation time increased, MeHgCl had obvious damage to cell morphology, decreased the ratio of Bcl-2 and Bak and increased the expressions of TNF-α, IL-6 and IL-1ß significantly. Furthermore, the expressions of IL-1ß and IL-6 in HgCl2 group were increased significantly in 6 h and 24 h. The apoptotic rates in MeHgCl and HgCl2 group were respectively higher than ß-HgS with 32.2% and 7.30% in 24 h. Our findings indicate that ß-HgS is much less neurotoxicity than MeHgCl and HgCl2 in Neuro-2a cells.

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats.

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats' cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.

Photography's Underappreciated Contributions to Neuropsychiatry: The Photographs of W. Eugene Smith in Minamata, Japan.

Photographers and filmmakers have made important contributions to the international mental health community through documentation and social commentary, leveraging the power of visual imagery. To illustrate, this article uses the example of W. Eugene Smith who photographed the catastrophic effects of methylmercury poisoning from industrial pollution in the region around Minamata Bay, Japan. Although many art forms have been comfortably integrated into mainstream psychiatry and neuropsychiatry, photography has been underappreciated and underutilized.

Aqueous Coriandrum sativum L. extract promotes neuroprotection against motor changes and oxidative damage in rat progeny after maternal exposure to methylmercury.

This study aimed to investigate the effects of Coriandrum sativum aqueous extract (CSAE) on the rat progeny of mothers exposed to methylmercury (MeHg). The presence of bioactive compounds and CSAE's antioxidant capacity been evaluated, and the offspring were assessed for their total mercury levels, motor behavioral parameters and oxidative stress in the cerebellum. The analysis of the bioactive compounds revealed significant amounts of polyphenols, flavonoids, and anthocyanins, as well as a variety of minerals. A DPPH test showed the CSAE had important antioxidant activity. The MeHg + CSAE group performed significantly better spontaneous locomotor activity, palmar grip strength, balance, and motor coordination in behavioral tests compared the MeHg group, as well as in the parameters of oxidative stress, with similar results to those of the control group. The MeHg + CSAE group also had significantly reduced mercury levels in comparison to the MeHg group. Based on the behavioral tests, which detected large locomotor, balance, and coordination improvements, as well as a reduction in oxidative stress, we conclude that CSAE had positive functional results in the offspring of rats exposed to MeHg.

Comparative Neuroprotective Effect of Celosia argentea Linn. and Vitamin E on Mercury-induced Oxidative and Histological Parameters of Rat Brain.

Mercury contamination of our environment in Nigeria is increasing as mining activity increases. Its exposure causes human toxicological effects which include neurotoxicity through reactive oxygen species. This study investigated the ameliorative effects of the flavonoid-rich aqueous extract of Celosia argentea (AECA) and vitamin E (VitE) in the brain of rats treated with mercuric chloride (HgCl2). Twenty-five adult male Wistar rats were randomized into five treatment groups (n=5). Group 1- control; Group 2- HgCl2 (4 mg/kg); Group 3- AECA (400 mg/kg); Group 4- HgCl2 (4 mg/kg) + AECA (400 mg/kg); Group 5- HgCl2 (4 mg/kg) + VitE (500 mg/kg). All items were administered using an oral cannula daily for 14 days. Behavioural studies were carried out on the 16th day of experiment after which rats were euthanized. Thereafter, gross, haematological and biochemical parameters [malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)] were assessed. Mercuric chloride significantly (p<0.05) reduced body weight of rats, SOD activity and GSH level but increased MDA level, CAT activity and the number of degenerated neurons in the cerebral cortex relative to control group. Microscopically, HgCl2 induced degeneration of cerebral cortical neurons and Purkinje neurons of the cerebellum. Treatment of HgCl2 and AECA and VitE caused a reversal of these HgCl2-induced alterations. The behavioural and haematological parameters were not significantly affected through the groups. The results suggest Celosia argentea Linn and vitamin E protected against mercury-induced gross, oxidative, cerebral and cerebellar damage. Both AECA and Vitamin E demonstrated neuroprotection in this experiment.

Nanoelemental selenium alleviated the mercury load and promoted the formation of high-molecular-weight mercury- and selenium-containing proteins in serum samples from methylmercury-poisoned rats.

Selenite (Se4+) has been found to counteract the neurotoxicity of methylmercury (MeHg) in MeHg-poisoned rats. However, Se4+ has narrow range between its toxic and beneficial effects. Nanoelemental selenium (SeNPs) was found to be less toxic than other forms of Se such as Se4+. In this study, the effects of SeNPs on the load of mercury (Hg) in rats were investigated. Hyphenated technique based on size-exclusion chromatography coupled with UV and inductively coupled plasma mass spectrometry (SEC-ICP-MS) detection and synchrotron radiation X-ray fluorescence spectroscopy (SR-XRF) were used to analyze the Hg-Se-containing proteins in the serum from MeHg-poisoned rats. The Hg-Se-containing fractions monitored by UV and ICP-MS were further characterized by MALDI-TOF-MS. Elevated serum Hg and Se levels were found in MeHg-poisoned rats after SeNPs treatment. Three main Hg-containing bands with molecular weights (MWs) of 25, 62 and 140 kDa were detected in the control samples. Treatment with SeNPs increased the Hg content in proteins at 62 and 170 kDa and decreased the Hg content at 25 kDa. The fraction with 25 kDa was assigned to metallothioneins (MTs), and fractions with 40 and 75 kDa were assigned to albumin. This study showed that the low-toxicity SeNPs could reduce the Hg load in the tissues and promote the formation of high molecular weight Hg- and Se-containing proteins in MeHg-poisoned rats.

Hormesis of mercuric chloride-human serum albumin adduct on N9 microglial cells via the ERK/MAPKs and JAK/STAT3 signaling pathways.

Mercury chloride (HgCl2), a neurotoxicant that cannot penetrate the blood-brain barrier (BBB). Although when the BBB are got damaged by neurodegenerative disorders, the absorbed HgCl2, mainly in form of Hg (II)-serum albumin adduct (Hg-HSA) in human plasma, can penetrate BBB and affect central nervous system (CNS) cells. Current study planned to evaluate the effect of Hg-HSA on the physiological function of N9 microglial cells. At low dosage (15 ng/mL) of Hg-HAS, the observed outcomes was: promoted cell propagation, Nitric Oxide (NO) and intracellular Ca2+ levels enhancement, suppressed the release of TNF-α and IL-1ß and inhibited cell proliferation. At high dosage (15 µg/mL) we observed decline in NO and intracellular Ca2+ levels, and increment in the release of TNF-α and IL-1ß. These biphasic effects are similar to hormesis, and the hormesis, in this case, was executed through ERK/MAPKs and JAK/STAT3 signaling pathways. Study of quantum chemistry revealed that Hg2+ could form stable coordination structures in both Asp249 and Cys34 sites of HSA. Although five-coordination structure in Asp249 site is more stable than four-coordination structure in Cys34 site but four-coordination structure is formed easily in-vivo in consideration of binding-site position in spatial structure of HSA.

Metal chelators and neurotoxicity: lead, mercury, and arsenic.

This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion.

Chemical Speciation of Selenium and Mercury as Determinant of Their Neurotoxicity.

The antagonism of mercury toxicity by selenium has been well documented. Mercury is a toxic metal, widespread in the environment. The main target organs (kidneys, lungs, or brain) of mercury vary depending on its chemical forms (inorganic or organic). Selenium is a semimetal essential to mammalian life as part of the amino acid selenocysteine, which is required to the synthesis of the selenoproteins. This chapter has the aim of disclosing the role of selenide or hydrogen selenide (Se-2 or HSe-) as central metabolite of selenium and as an important antidote of the electrophilic mercury forms (particularly, Hg2+ and MeHg). Emphasis will be centered on the neurotoxicity of electrophile forms of mercury and selenium. The controversial participation of electrophile mercury and selenium forms in the development of some neurodegenerative disease will be briefly presented. The potential pharmacological use of organoseleno compounds (Ebselen and diphenyl diselenide) in the treatment of mercury poisoning will be considered. The central role of thiol (-SH) and selenol (-SeH) groups as the generic targets of electrophile mercury forms and the need of new in silico tools to guide the future biological researches will be commented.

Is mercury in Tibetan Medicine toxic? Clinical, neurocognitive and biochemical results of an initial cross-sectional study.

Mercury an important therapeutic substance in Tibetan Medicine undergoes complex "detoxification" prior to inclusion in multi-ingredient formulas. In an initial cross-sectional study, patients taking Tibetan Medicine for various conditions were evaluated for mercury toxicity. Two groups were identified: Group 1, patients taking " Tsothel" the most important detoxified mercury preparation and Group 2, patients taking other mercury preparations or mercury free Tibetan Medicine. Atomic fluorescence spectrometry of Tibetan Medicine showed mercury consumption 130 µg/kg/day (Group 1) and 30 µg/kg/day (Group 2) ( P ≤ 0.001), levels above EPA (RfDs) suggested threshold (0.3 µg/kg /day) for oral chronic exposure. Mean duration of Tibetan Medicine treatment was 9 ± 17 months (range 3-116) (Group 1) and 5 ± 1.96 months (range 1-114) (Group 2) (NS) with cumulative days of mercury containing Tibetan Medicine, 764 days ± 1214 (range 135-7330) vs. 103 days ± 111 (range 0-426), respectively ( P ≤ 0.001). Comparison of treatment groups with healthy referents (Group 3) not taking Tibetan Medicine showed no significant differences in prevalence of 23 non-specific symptoms of mercury toxicity, abnormal neurological, cardiovascular and dental findings and no correlation with mercury exposure variables; consumption, cumulative treatment days, blood/ urine Hg. Liver and renal function tests in treatment groups were not significantly increased compared to referents, with mean urine Beta2 Microglobulin within the normal range and not significantly associated with Hg exposure variables after correcting for confounding variables. Neurocognitive testing showed no significant intergroup differences for Wechsler Memory Scale, Grooved Pegboard, Visual Retention, but Group1 scores were better for Mini-Mental, Brief Word Learning, Verbal Fluency after correcting for confounding variables. These results suggest mercury containing Tibetan Medicine does not have appreciable adverse effects and may exert a possible beneficial effect on neurocognitive function. Since evidence of mercury as a toxic heavy metal, however, is well known, further analysis of literature on mercury use in other Asian traditional systems is highly suggested prior to further studies.

Three Case Reports of Successful Vibration Therapy of the Plantar Fascia for Spasticity Due to Cerebral Palsy-Like Syndrome, Fetal-Type Minamata Disease.

Fetal-type Minamata disease is caused by the exposure to high concentrations of methylmercury in the fetal period and shows cerebral palsy-like clinical features. Relief of spasticity is a major task of rehabilitation to improve their activities of daily living. Here we report the effect of long-term vibration therapy on bilateral lower-limb spasticity in 3 patients with fetal-type Minamata disease. We used a simple, inexpensive, and noninvasive approach with hand-held vibration massagers, which were applied to the plantar fascia at 90 Hz for 15 minutes. The effect was observed soon after the first treatment and resulted in better performance of the repetitive facilitation. Vibration therapy for 1 year improved Modified Ashworth Scale for the ankle flexors in 2 cases. The labored gait improved and gait speed increased in another case. Continued vibration therapy for another 1 year further improved Modified Ashworth Scale score and range of motion of ankle dorsiflexion in 1 case. This case showed the decreased amplitude of soleus H-reflex after the 15-minute vibration therapy, suggesting that α-motor neuron excitability was suppressed. Vibration therapy using a hand-held vibration massager may offer safe and effective treatment for lower-limb spasticity in patients with chronic neurological disorders.

Methylmercury exposure and neurological outcomes in Taiji residents accustomed to consuming whale meat.

Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to the central nervous system. In Japan, industrial emission of MeHg has resulted in MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans are exposed to MeHg derived from natural sources, primarily fish and fish predators. Therefore, MeHg continues to be an environmental risk to human health, particularly in susceptible populations that frequently consume substantial amounts of fish or fish predators such as whale. This study aimed to investigate the health effects of MeHg exposure in adults. The subjects were 194 residents (117 males, 77 females; age 20-85 years) who resided in the coastal town of Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for mercury content and performed detailed neurological examinations and dietary surveys. Audiometry, magnetic resonance imaging, and electromyography were performed to diagnose neurological defects. Whole blood mercury and selenium (Se) levels were measured in 23 subjects. The geometric mean of the hair mercury levels was 14.9 µg/g. Twelve subjects revealed hair mercury levels >50 µg/g (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale meat intake. These results suggested that residents in Taiji were highly exposed to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression analysis demonstrated no significant correlations between hair mercury levels and neurological outcomes, whereas some of the findings significantly correlated with age. A significantly positive correlation between whole blood mercury and Se levels was observed and the whole blood mercury/Se molar ratios of all subjects were <1. These findings suggested that sufficient Se intake might be one of causes of the absence of adverse effects of MeHg exposure in this study.

Commentary on the abuse of metal chelation therapy in patients with autism spectrum disorders.

Approximately half a million patients with autism spectrum disorders are subjected to chelation therapy in the US annually. The overwhelming majority of such cases are chelated for non-accepted medical indications. These patients may seek evaluation when a urine sample is assayed after the administration of a chelating agent and the values obtained have been improperly compared to references ranges for non-chelated urines, causing falsely elevated results. Legitimate practitioners confronted with such data must decide, preferably in consultation with the patient or their guardian(s), whether to do further testing using legitimate methodology or to simply dismiss the results of the improper testing. Bayesian principles tell us that further testing is likely to yield results within normal reference ranges. However, under some circumstances, it is useful to do such testing in order to demonstrate that there is no need for chelation therapy. Unnecessary chelation therapy is expensive, can cause significant acute adverse effects, and may be associated with long-term consequences.

Response inhibition is impaired by developmental methylmercury exposure: acquisition of low-rate lever-pressing.

Developmental methylmercury (MeHg) exposure produces response perseveration on discrimination reversal procedures, disrupts sensitivity to reinforcement, and enhances sensitivity to dopamine agonists - a profile suggesting a deficit in behavioral inhibition. To examine inhibition, we examined MeHg's effects on the acquisition and persistence of low-rate lever-pressing following a history of high-rate responding. Additionally, we examined whether chronic exposure to selenium protects against MeHg's developmental neurotoxicity. Female rats were exposed in utero via maternal exposure to drinking water containing 0ppm, 0.5ppm or 5ppm of Hg as MeHg, producing approximately 0µg/kg/day, 40µg/kg/day, or 400µg/kg/day of Hg. The mothers (during gestation) and the offspring (throughout life) consumed a purified diet containing 0.06ppm or 0.6ppm of Se (as sodium selenite), forming a 2 (lifespan diet)×3 (developmental MeHg) factorial design. Adult offspring lever-pressed under two schedules of reinforcement. A differential reinforcement of high-rate (DRH) schedule imposed rigid response requirements that remained constant through the study. A high-rate percentile schedule (PCNT-H) incorporated a flexible criterion that reinforced short interresponse times using an adjusting criterion that was sensitive to recent performance. After high-rate responding stabilized, the PCNT-H schedule was abruptly inverted by reinforcing long interresponse times. Acquisition of low-rate responding was impaired in the MeHg-exposed rats because of intrusions of high-rate response bursts. DRH response rates did not change. Dietary selenium did not influence MeHg's effects. High-rate operant behavior perseverated, suggesting that gestational MeHg exposure impairs response inhibition - an effect that extends results previously reported using choice procedures or spatial and visual discrimination reversals.

Visual evoked potentials in children prenatally exposed to methylmercury.

Prenatal exposure to methylmercury can cause both neurobehavioral deficits and neurophysiological changes. However, evidence of neurotoxic effects within the visual nervous system is inconsistent, possibly due to incomplete statistical adjustment for beneficial nutritional factors. We evaluated the effect of prenatal methylmercury exposure on visual evoked potential (VEP) latencies in Faroese children with elevated prenatal methylmercury exposure. A cohort of 182 singleton term births was assembled in the Faroe Islands during 1994-1995. At age 7 years, VEP tracings were obtained from 139 cohort subjects after exclusion of subjects with abnormal vision conditions. We used multiple regression analysis to evaluate the association of mercury concentrations in cord blood and maternal hair at parturition with VEP latencies after adjustment for potential confounders that included the cord-serum phospholipid concentration of n-3 polyunsaturated fatty acids (PUFAs) and the duration of breastfeeding. Unadjusted correlations between mercury exposure and VEP latencies were equivocal. Multiple regression models showed that increased mercury concentrations, especially in maternal hair, were associated with delayed latencies for VEP peak N145. After covariate adjustment, a delay of 2.22 ms (p=0.02) was seen for each doubling of the mercury concentration in maternal hair. In agreement with neuropsychological findings, the present study suggests that prenatal methylmercury exposure may have an adverse effect on VEP findings despite the absence of clinical toxicity to the visual system. However, this association was apparent only after adjustment for n-3 PUFA status.

Glutathione-mediated neuroprotection against methylmercury neurotoxicity in cortical culture is dependent on MRP1.

Methylmercury (MeHg) exposure at high concentrations poses significant neurotoxic threat to humans worldwide. The present study investigated the mechanisms of glutathione-mediated attenuation of MeHg neurotoxicity in primary cortical culture. MeHg (5 µM) caused depletion of mono- and disulfide glutathione in neuronal, glial and mixed cultures. Supplementation with exogenous glutathione, specifically glutathione monoethyl ester (GSHME) protected against the MeHg induced neuronal death. MeHg caused increased reactive oxygen species (ROS) formation measured by dichlorodihydrofluorescein (DCF) fluorescence with an early increase at 30 min and a late increase at 6h. This oxidative stress was prevented by the presence of either GSHME or the free radical scavenger, trolox. While trolox was capable of quenching the ROS, it showed no neuroprotection. Exposure to MeHg at subtoxic concentrations (3 µM) caused an increase in system x(c)(-) mediated (14)C-cystine uptake that was blocked by the protein synthesis inhibitor, cycloheximide (CHX). Interestingly, blockade of the early ROS burst prevented the functional upregulation of system x(c)(-). Inhibition of multidrug resistance protein-1 (MRP1) potentiated MeHg neurotoxicity and increased cellular MeHg. Taken together, these data suggest glutathione offers neuroprotection against MeHg toxicity in a manner dependent on MRP1-mediated efflux.

Hyperintense lesions in brain MRI after exposure to a mercuric chloride-containing skin whitening cream.

Exposure to inorganic mercury (Hg) is a serious problem presenting with a combination of neurological and psychiatric symptoms along with weight loss, pruritus, erythema, arterial hypertension, tachycardia, and renal tubular dysfunction. We report a 4-year-old girl with chronic intoxication of inorganic mercury secondary to the accidental use of an Hg2Cl2- and HgCl2-containing skin whitening cream (urine level of Hg, 41.1 µg/l; reference level, < 25 µg/l). Under treatment with dimercapto-1-propansulficacid, Hg level in the urine raised to 1,175.5 µg/l, neurological deterioration occurred, and brain magnetic resonance imaging (MRI) showed on fluid attenuated inversion recovery sequences new hyperintense lesions in the subcortical white matter. After 4 months, clinical signs and symptoms and brain MRI findings resolved. This is a first case of inorganic mercury poisoning showing hyperintense lesions in brain MRI and confirms earlier cases showing transient deterioration during chelation therapy. Although urinary excretion could be enhanced during chelation therapy, signs and symptoms of intoxication could be worsened.

The in vitro effects of Trolox on methylmercury-induced neurotoxicity.

Methylmercury (MeHg), an environmental toxicant primarily found in fish and seafood poses a dilemma to both consumers and regulatory authorities given the nutritional benefits of fish consumption vs. possible adverse neurological damage caused by MeHg. The present study addresses whether supplementation with 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), alters the neuro-oxidative effects of MeHg in C6-glioma and B35-neuronal cell lines. As indicators of cytotoxicity, reduced glutathione (GSH), reactive oxygen species (ROS) and mitochondrial activity (MTT) were measured. The cellular mercury (Hg) content was measured with high resolution-inductively coupled plasma mass spectrometry (HR-ICPMS). The amount of MeHg-induced ROS was significantly reduced (p<0.05) after treatment with 50muM Trolox in C6 glial cell line. However, treatment with Trolox did not induce any significant increase in GSH levels or MTT activity in either of the cell lines. In addition, treatment with Trolox did not induce any significant changes in intracellular MeHg levels. The MeHg and Trolox treated C6 glial cell line differed significantly (p<0.05) from the B35 cell line for MTT, ROS and GSH activity. These findings provide experimental evidence that preincubation with Trolox prevents MeHg-induced ROS generation in C6 glial cell line by quenching of free radicals and not by changes in intracellular GSH or MeHg content.

The chemical nature of mercury in human brain following poisoning or environmental exposure.

Methylmercury is among the most potentially toxic species to which human populations are exposed, both at high levels through poisonings and at lower levels through consumption of fish and other seafood. However, the molecular mechanisms of methylmercury toxicity in humans remain poorly understood. We used synchrotron X-ray absorption spectroscopy (XAS) to study mercury chemical forms in human brain tissue. Individuals poisoned with high levels of methylmercury species showed elevated cortical selenium with significant proportions of nanoparticulate mercuric selenide plus some inorganic mercury and methylmercury bound to organic sulfur. Individuals with a lifetime of high fish consumption showed much lower levels of mercuric selenide and methylmercury cysteineate. Mercury exposure did not perturb organic selenium levels. These results elucidate a key detoxification pathway in the central nervous system and provide new insights into the appropriate methods for biological monitoring.