Methylmercury Exposure Research Articles

Prenatal low-dose methylmercury exposure causes premature neuronal differentiation and autism-like behaviors in a rodent model

Aberrant neurodevelopment is a core deficit of autism spectrum disorder (ASD). Here we ask whether a non-genetic factor, prenatal exposure to the environmental pollutant methylmercury (MeHg), is a contributing factor in ASD onset. We showed that adult mice prenatally exposed to non-apoptotic MeHg exhibited key ASD characteristics, including impaired communication, reduced sociability, and increased restrictive repetitive behaviors, whereas in the embryonic cortex, prenatal MeHg exposure caused premature neuronal differentiation. Further single-cell RNA sequencing (scRNA-seq) analysis disclosed that prenatal exposure to MeHg resultedin cortical radial glial precursors (RGPs) favoring asymmetric differentiation to directly generate cortical neurons, omitting the intermediate progenitor stage. In addition, MeHg exposure in cultured RGPs increased CREB phosphorylation and enhanced the interaction between CREB and CREB binding protein (CBP). Intriguingly, metformin, an FDA-approved drug, can reverse MeHg-induced premature neuronal differentiation via CREB/CBP repulsion. These findings provide insights into ASD etiology, its underlying mechanism, and a potential therapeutic strategy.

The association of auditory function measures with low-level methylmercury from oceanic fish consumption and mercury vapor from amalgam: The Seychelles Child Development Study Nutrition 1 Cohort

BackgroundSome authors have reported that low-level exposure to methylmercury (MeHg) adversely impacts measures of auditory function. These reports, however, are not consistent in their findings. Consequently, we examined auditory function in a population exposed to low-level methylmercury (MeHg) exposure from fish consumption and to mercury vapor (Hg0) from dental amalgams. We analyzed their associations with the participants hearing acuity, absolute and interwave ABR latencies, and otoacoustic emissions (distortion product/DPOAE and click evoked/CEOAE). DesignWe administered an audiometry test battery to 246 participants from the Seychelles Child Development Study (SCDS) Nutrition Cohort 1 (NC1) at 9 years of age. The test battery included standard pure-tone audiometry, tympanometry, Auditory Brainstem Responses (ABR) and Distortion Product and Click Evoked Otoacoustic Emissions (DPOAE and CEOAE) testing. We measured prenatal MeHg exposure in maternal hair and postnatal MeHg in children’s hair. We approximated prenatal Hg0 exposure using maternal amalgam surface area and postnatal Hg0 using children amalgam surface area. Complete exposure records and audiometric data were available on 210 participants and in them we analyzed the association of MeHg and Hg0 exposures with auditory outcomes using covariate-adjusted linear regression models adjusted for sex and tympanometric pressure. ResultsHg exposures were similar for both sexes. Seven of the 210 evaluable participants examined had either a mild (5) or moderate (2) hearing loss. Four had a mild monaural hearing loss and 3 had either a mild (1) or moderate (2) bilateral hearing loss. No participant had greater than a moderate hearing loss in either ear. Hg exposures were higher in participants with either a mild or moderate hearing loss, but these differences were not statistically significant. Among the 210 with complete data, neither prenatal nor postnatal MeHg nor Hg0 exposure was statistically significantly associated with any of the ABR endpoints (p > 0.05 for all 72 associations). Neither prenatal nor postnatal Hg0 exposure was associated with any of the OAE endpoints (p > 0.05). MeHg exposure was statistically associated with 6 of the 56 DPOAE endpoints (p-values between 0.0001 and 0.023), but none of the 40 CEOAE endpoints. Two of the associations occurred with prenatal MeHg exposures and 1 of those would suggest a beneficial effect. Four of the other associations occurred with postnatal MeHg exposures with only 2 found in left ears of both males and females and the other 2 in the left and right ear of females at only one frequency. ConclusionOverall, these data do not present a clear and consistent pattern to suggest that the auditory system is negatively affected by low-level methylmercury exposure due to dietary consumption of oceanic fish or mercury vapor exposure from dental amalgams.

Associations between mercury exposure with blood pressure and lipid levels: A cross-sectional study of dental professionals

Mercury (Hg) exposure is a public health problem worldwide that is now being addressed through the Minamata Convention on Mercury. Fish containing methylmercury and dental amalgam containing elemental Hg are the major sources of exposure for most populations. There is some evidence that methylmercury impacts cardiovascular and metabolic health, primarily in populations with high exposure levels. Studies of elemental Hg and these outcomes are relatively rare. We aimed to examine associations between Hg exposure (both elemental and methylmercury) and blood pressure, as well as cholesterol and triglyceride levels. In 2012, we recruited dental professionals attending the Health Screening Program at the American Dental Association (ADA) Annual Session in California. Total Hg levels in hair and blood samples were analyzed as indicators of methylmercury exposure and in urine as an indicator of primarily elemental Hg exposure (n = 386; mean ± sd age 55 ± 11 years). We measured blood pressure (systolic and diastolic) and lipid profiles (total cholesterol, high-density lipoprotein cholesterol [HDL], low-density lipoprotein cholesterol [LDL] and triglycerides). The geometric means (geometric standard deviations) for blood, hair, and urine Hg were 3.64 (2.39) μg/L, 0.60 (2.91) μg/g, and 1.30 (2.44) μg/L, respectively. For every one μg/L increase in specific gravity-adjusted urine Hg, LDL increased by 2.31 mg/dL (95% CI = 0.09, 4.54), in linear regression adjusting for BMI, race, sex, polyunsaturated fatty acid intake from fish consumption, smoking status, and use of cholesterol-lowering medication. No significant associations between Hg biomarkers and blood pressure or hair or blood Hg with lipid levels were observed. Results suggest that elemental Hg exposure may influence LDL concentrations in adults with low-level exposure, and this relationship merits further study in other populations.

Alterations in UPR Signaling by Methylmercury Trigger Neuronal Cell Death in the Mouse Brain

Methylmercury (MeHg), an environmental toxicant, induces neuronal cell death and injures specific areas of the brain. MeHg is known to induce oxidative and endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) pathway has a dual nature in that it regulates and protects cells from an overload of improperly folded proteins in the ER, whereas excessively stressed cells are eliminated by apoptosis. Oxidative stress/ER stress induced by methylmercury exposure may tilt the UPR toward apoptosis, but there is little in vivo evidence of a direct link to actual neuronal cell death. Here, by using the ER stress-activated indicator (ERAI) system, we investigated the time course signaling alterations of UPR in vivo in the most affected areas, the somatosensory cortex and striatum. In the ERAI-Venus transgenic mice exposed to MeHg (30 or 50 ppm in drinking water), the ERAI signal, which indicates the activation of the cytoprotective pathway of the UPR, was only transiently enhanced, whereas the apoptotic pathway of the UPR was persistently enhanced. Furthermore, detailed analysis following the time course showed that MeHg-induced apoptosis is strongly associated with alterations in UPR signaling. Our results suggest that UPR modulation could be a therapeutic target for treating neuropathy.

Developmental Methylmercury Exposure Induced and Age-Dependent Glutamatergic Neurotoxicity in Caenorhabditis elegans.

Developmental methylmercury (MeHg) exposures cause latent neurotoxic effects in adults; however, the mechanisms underlying the latent neurotoxicity are not fully understood. In the current study, we used C. elegans as an animal model to investigate the latent neurotoxic effects of developmental MeHg exposures on glutamatergic neurons. The young larvae stage 1 worms were exposed to MeHg (0.05 ~ 5 µM) for 48h. The morphological and behavioral endpoints of glutamatergic neurons were compared when worms reached to adult stages including the young adult stage (day 1 adult) and the old adult stage (day 10 adult). Here, we showed that C. elegans glutamatergic neurons were morphologically intact following low or medium MeHg exposures (0.05 ~ 0.5 µM). The morphological damage of glutamatergic neurons appeared to be pronounced in day 10 adults developmentally exposed to 5 µM MeHg. Behavioral assays also showed an age-dependent latent effect of MeHg. In the nose touch response assay, only day 10 adult worms exhibited a functional decline following prior 5 µM MeHg exposure. Moreover, the disruption of NaCl memory appeared only in day 1 adults following MeHg exposures but not in day 10 adults. The expression of C. elegans homologs of mammalian vesicular glutamate transporter (eat-4) was repressed in day 1 adults, while the glutamate receptor homolog (glr-1) was upregulated in day 10 adults with 5 µM MeHg. In the comparison of age-dependent changes in the insulin-like pathway (daf-2/age-1/daf-16) following MeHg exposures, we showed that the daf-2/age-1/daf-16 pathway was mobilized in day 1 adults but repressed in day 10 adults. Collectively, our data supports a conclusion that MeHg-induced glutamatergic neurotoxicity exhibits an age-dependent pattern, possibly related to the prominent changes in age-dependent modulation in the glutamatergic neurotransmission and metabolic pathways.

Necrotic-like BV-2 microglial cell death due to methylmercury exposure.

Methylmercury (MeHg) is a dangerous environmental contaminant with strong bioaccumulation in the food chain and neurotoxic properties. In the nervous system, MeHg may cause neurodevelopment impairment and potentially interfere with immune response, compromising proper control of neuroinflammation and aggravating neurodegeneration. Human populations are exposed to environmental contamination with MeHg, especially in areas with strong mining or industrial activity, raising public health concerns. Taking this into consideration, this work aims to clarify pathways leading to acute toxic effects caused by MeHg exposure in microglial cells. BV-2 mouse microglial cells were incubated with MeHg at different concentrations (0.01, 0.1, 1 and 10µM) for 1h prior to continuous Lipopolysaccharide (LPS, 0.5μg/ml) exposure for 6 or 24h. After cell exposure, reactive oxygen species (ROS), IL-6 and TNF-α cytokines production, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) release, metabolic activity, propidium iodide (PI) uptake, caspase-3 and -9 activities and phagocytic activity were assessed. MeHg 10µM decreased ROS formation, the production and secretion of pro-inflammatory cytokines IL-6, TNF-α, iNOS immunoreactivity, the release of NO in BV-2 cells. Furthermore, MeHg 10µM decreased the metabolic activity of BV-2 and increased the number of PI-positive cells (necrotic-like cell death) when compared to the respective control group. Besides, MeHg did not interfere with caspase activity or the phagocytic profile of cells. The short-term effects of a high concentration of MeHg on BV-2 microglial cells lead to impaired production of several pro-inflammatory mediators, as well as a higher microglial cell death via necrosis, compromising their neuroinflammatory response. Clarifying the mechanisms underlying MeHg-induced neurotoxicity and neurodegeneration in brain cells is relevant to better understand acute and long-term chronic neuroinflammatory responses following MeHg exposure.

Identifying susceptibility factors for methylmercury-induced developmental neurotoxicity

Background and aim: Methylmercury (MeHg) exposures during pregnancy or childhood can cause developmental neurotoxicity (DNT), including cognitive, behavioral, and other effects. While many studies have reported on these effects, fewer have examined other factors that contribute to susceptibility to MeHg-induced DNT. The first objective of this project is to determine whether there are demographic, biological, psychosocial, societal, environmental, or other factors that may make developmentally exposed individuals more susceptible to these effects. A second objective is to develop a replicable approach for identifying susceptibility data in assessments of the health effects of chemicals. Methods: A systematic literature search for 2019-2021 aimed to identify all epidemiology studies that examined methylmercury exposure and DNT. Identified studies were then screened for susceptibility information at the title/abstract and full text levels by two reviewers. A search string was also developed and applied to title/abstracts to determine whether these studies could be identified without extensive screening. Susceptibility information was then summarized. Results: Data examining several potential susceptibility factors for MeHg were identified, including genetic polymorphisms, sex, maternal factors, nutritional status, and multi-chemical exposures. Conclusion: This project identifies potential susceptibility factors associated with MeHg and DNT. The methods applied to MeHg may be adapted and utilized for identifying and interpreting the literature on susceptibility factors for adverse health effects from other chemical exposures. Keywords: methylmercury, developmental neurotoxicity, susceptibility, systematic review, environmental justice Disclaimer: The views expressed in this abstract are those of the author and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency.

Global research trends on maternal exposure to methylmercury and offspring health outcomes.

This study aimed to analyze the landscape of maternal methylmercury exposure and its offspring consequences based on knowledge mapping of the 100 most-cited papers about this theme. A search was performed using the Web of Science, without any restriction of language or publication year. Data bibliometrics, such as the number of citations, citation density, corresponding author’s country, year of publication, study design, and keywords, were extracted from each paper and analyzed. VOSviewer software was used to create graphical bibliometric maps. Of a total of 1,776 studies on this theme, the 100 most-cited papers rendered the number of citations ranged from 110 to 1,356 citations. The non-systematic reviews and cohort studies from Anglo-Saxon countries published in the first decade of the 2000s were the most frequent. Clarkson, Grandjean, and Myers were the authors with higher citation density. A total of 520 keywords represented the evolution of the theme, from classic episodes of MeHg intoxication, as well as main the health changes until the different forms of exposure and, in recent years, biomonitoring studies were highlighted. Our findings provide the global research trends highlighting the network of most influential authors and a better understanding of the evolution and future scenarios of this theme.

Impacts of neonatal methylmercury on behavioral flexibility and learning in spatial discrimination reversal and visual signal detection tasks

Early postnatal development in rodents is sensitive to neurotoxic effects of the environmental contaminant, methylmercury. While juvenile and adolescent exposure also produce long-term impairments in behavior, the outcome of neonatal exposure is less understood. Neural development during the neonatal period in rodents is akin to that seen in humans during the third trimester of pregnancy but methylmercury exposure occurring during the neonatal period has not been modeled, partly because breast milk is a poor source of bioavailable methylmercury. To examine this developmental period, male Long-Evans rats were exposed to 0, 80, or 350 µg/kg/day methylmercuric chloride from postnatal days 1–10, the rodent neonatal period. As adults, behavioral flexibility, attention, memory, and expression of the dopamine transporter in these rats was assessed. Rats exhibited changes in behavioral flexibility assessed in a spatial discrimination reversal procedure. Those rats exposed to the highest dose of methylmercury displayed subtly altered patterns of perseveration compared to control animals. During acquisition of the attention/memory procedure, rats exposed to this dose also had slower acquisition, and achieved lower overall accuracy during training, compared to controls despite neither attention nor memory being affected once the task was acquired. Finally, dopamine transporter expression in the striatum, prefrontal cortex, and hippocampus was unchanged in these adult rats. The results of this study replicate the trend of findings seen with exposure during gestation or during adolescence.

The First Exposure Assessment of Mercury Levels in Hair among Pregnant Women and Its Effects on Birth Weight and Length in Semarang, Central Java, Indonesia.

(1) Background: Methylmercury (MeHg) exposure during pregnancy is an important issue due to its possible adverse health effects on fetus. To contribute the development of assessment system of Hg exposure through fish consumption and health effects on children, we examined the hair Hg levels in pregnant women and birth weight and length. (2) Methods: In 2018, a cohort study was conducted on 118 pregnant women-infant pairs from six community health centers in the northern coastal area in Central Java Indonesia. Data on mothers’ characteristics during pregnancy, birth outcomes, and fish consumption were collected. Total Hg concentrations were determined from hair samples. (3) Results: The median (min-max) of the maternal hair Hg level was 0.434 (0.146–8.105) µg/g. Pregnant women living in lowland areas, near the sea, showed higher hair Hg concentration and fish consumption than those in highland areas {[0.465 (0.146–8.105) vs. 0.385 (0.150–1.956) µg/g; p = 0.043] and [(85.71 (0–500.0) vs. 49.76 (0.0–428.57) g/day; p < 0.01], respectively}. The maternal hair Hg level had no association with baby’s birth weight and length. (4) Conclusions: The median maternal hair Hg is at a low level and had no association with infant birth weight and length in this study subjects.

Hair methylmercury levels are inversely correlated with arterial stiffness

Background and aimsCardiovascular diseases (CVD), including coronary heart disease, are the leading cause of death worldwide. Several studies investigating the relationship between fish intake, methylmercury exposure, and CVDs in adults have reported inconsistent results. This study aimed to determine the association between hair methylmercury levels and arterial stiffness using brachial–ankle pulse wave velocity (baPWV). MethodsThis cross-sectional study included 891 seemingly healthy Korean adults (418 men and 473 women). The anthropometric and biochemical profiles, including methylmercury levels in the hair, were measured. Arterial stiffness was measured using baPWV, wherein high baPWV was defined as >1375 cm/s (>75th percentile). The odds ratios for high baPWVs were examined using multivariable logistic regression analysis after adjusting for potential confounders across the quintiles of hair methylmercury levels (Q1 = ≤0.6, Q2 = 0.6–0.8, Q3 = 0.8–1.1, Q4 = 1.1–1.5, and Q5=>1.5 μg/g). ResultsAfter adjusting for multiple confounders-age, sex, height, body weight, smoking status, weekly alcohol consumption, total metabolic equivalent of task, mean arterial blood pressure, resting heart rate, triglycerides, low density lipoprotein cholesterol, fasting plasma glucose, uric acid and white blood cell count-the odds ratios (95% confidence intervals) for high baPWVs in each quintile of hair methylmercury levels were 1.00, 0.36 (0.17–0.76), 0.38 (0.20–0.76), 0.28 (0.13–0.61), and 0.49 (0.24–0.99), respectively. ConclusionsWithin non-toxic low levels, higher hair methylmercury levels are independently associated with lower arterial stiffness in seemingly healthy Korean adults regardless of classical cardiovascular risk factors.

Methylmercury Risk Assessment Based on European Human Biomonitoring Data.

A risk assessment (RA) was conducted to estimate the risk associated with methylmercury (MeHg) exposure of vulnerable European populations, using Human Biomonitoring (HBM) data. This RA was performed integrating published data from European HBM surveys and earlier EFSA approaches (EFSA 2012). Children/adolescents (3 to 17 years old) and women of childbearing age (18 to 50 years old) were selected as relevant study population groups for this RA. Two types of HBM datasets were selected: HBM studies (n = 18) with mercury (Hg) levels (blood and hair, total Hg and/or MeHg) in the general population in different EU countries and the DEMOCOPHES harmonized study in child–mother pairs (hair, total Hg) in 17 EU countries as a reference. Two approaches were included in the RA strategy: the first one was based on estimations of the fraction of children/adolescents and women of childbearing age, respectively, from the EU general population exceeding the HBM-I value established by the German Human Biomonitoring Commission, measured as Hazard Quotients (HQ); and the second approach was based on estimations of the fraction of the two population groups exceeding the Tolerable Weekly Intake (TWI) (or their equivalent to Tolerable Daily Intake (TDI)) defined by EFSA in 2012. The HQ approach showed that for both groups, the risk varies across EU countries and that some EU areas are close to or exceeding the exposure guidance values. This is the case of Spain and Portugal, which showed the highest HQ (GM and/or P95), probably due to their higher fish consumption. Results from the EFSA approach show that hair values of children/adolescents and women of childbearing age (both in selected HBM studies and in DEMOCOPHES study) are below the TDI of 1.9 µg/g; therefore, in general, the European population does not exceed the daily average/intake dose for MeHg and/or Hg. A possible risk underestimation was identified in our assessment since for many studies no data on P95 were available, causing loss of relevant information for risk characterization on the upper bound. In addition, data from other European countries also with high seafood consumption, such as France, Greece or Iceland, were not available. For this reason, further RA refinement is needed with harmonized and more widespread HBM data to account for differences in European exposure and associated risks, so that interventions to protect vulnerable citizens, can be applied.

Multiple exposure to methylmercury aggravates DNA damage in the BTBR T + Itpr3 tf/J autistic mouse model: The role of DNA repair efficiency

Environmental and genetic factors have been recognized to play major roles in the pathogenesis of autism. Here we examined the BTBR T+Itpr3tf/J (BTBR) mice’s susceptibility, an autistic model, to the genotoxic effects and DNA repair dysregulation of methylmercury. Micronuclei formation and oxidative DNA damage were analyzed using the micronucleus/fluorescence in situ hybridization test and modified comet assay, respectively. The results showed higher centromeric-positive micronuclei and oxidative DNA damage in BTBR mice exposed to methylmercury than the unexposed mice, which indicates that mutagenesis aggravated in BTBR mice after methylmercury exposure. Lipid peroxides in BTBR mice were significantly elevated, with a decrease in reduced/oxidized glutathione ratio after methylmercury exposure, indicating an augmenting oxidant-antioxidant imbalance. The expression of several genes involved in DNA repair was markedly altered in BTBR mice after methylmercury exposure as evaluated via PCR array and RT-PCR analyses. Declining of the antioxidant defense and dysregulation in DNA repair process after methylmercury exposure may explain the aggravated genotoxic susceptibility of BTBR mice. Thus, autistic individuals exposed to methylmercury must be under regular medical follow-up through standard timetabled medical laboratory inquiry to allow for early recognition of any mutagenic changes. Additionally, strategies that elevate cellular antioxidants/DNA repair efficiency may counteract methylmercury-induced genotoxicity.

Potential risks and health benefits of fish in the diet during the childbearing period: Focus on trace elements and n-3 fatty acid content in commonly consumed fish species from the Adriatic Sea

Fish is important staple in the human diet and also a primary source of highly toxic methylmercury exposure. This study evaluates total mercury (THg), total arsenic (TAs) and selenium (Se) levels together with potential health risks and benefits of habitual fish diet in healthy postpartum women in coastal Croatia (n = 100). Self-reported fish intake habits were recorded by a semi-quantitative food frequency questionnaire. Elements were analyzed in maternal hair and blood/serum as well as in most frequently consumed fish specimens and products by inductively coupled plasma mass spectrometry and fatty acids, including eicosapentaenoic plus docosahexaenoic n-3 polyunsaturated fatty acids (EPA plus DHA), were determined in raw Adriatic fish by gas chromatography. The estimated average fish consumption frequency was 1.9 servings per week. Median THg levels above the European regulatory limit were reached only in wild Adriatic gilthead seabream. Maternal THg and TAs levels correlated positively with fish consumption (ρ = 0.262, 0.357 and 0.342, respectively) and serum Se was lower in cigarette smokers (p < 0.05). It was concluded that in women during the childbearing period 2–3 servings per week of commonly consumed fish species originated mostly from the Adriatic Sea provides the desired intake of beneficial micronutrients Se and EPA plus DHA. In sensitive subpopulations with habitual fish rich diet, species with high Hg content should be identified, such as wild Adriatic gilthead seabream recognized in this study for which is recommended that it should be consumed not more than once a week to prevent potential health risks.

Mercury in Dried Market Fish of Hong Kong and San Francisco: Human Health Implications

Asian, Asian Pacific Islanders, and Asian American residents of San Francisco have higher exposure to mercury and the associated health risks associated with methylmercury toxicity from fish consumption than other demographics across the United States. Due to their higher annual fish consumption, Hong Kong Chinese residents have elevated risks to methylmercury exposure. Objectives: We investigate samples of dried market fish from San Francisco and from Hong Kong as potential sources of mercury contamination in fish commonly consumed by Asian and Asian American residents. Methods: We analyze 81 samples of dried market fish from San Francisco and Hong Kong for mercury concentration using Inductively Coupled Plasma Emission Spectrograph and Processing Cold Vapor Atomic Fluorescence Spectrometry. We binned into market categories, trophic level, and habitat type for statistical analysis. Results: No significant difference was observed in the mercury levels of samples between San Francisco and Hong Kong (p-value = 0.47). Dried samples did show higher rates of mercury than wet samples reported by the FDA. Data from dried market fish samples also show evidence of bioaccumulation: the concentration of toxins in higher trophic levels of fish (p-value &lt; 0.01). Eliminating apex predators, nearly all samples of fish from both locations and from lower trophic levels had levels below the lowest health advisory thresholds of 0.5 ppm methylmercury by weight. Discussion: Dried fish samples from markets in San Francisco and Hong Kong showed mercury levels with the potential to exceed guidelines set by the EPA and the EFSA, but consumption rates are lacking to know if this threshold is actually being exceeded by consumers. We make recommendations regarding the health risks of dried market fish and of consuming or avoiding fish from certain trophic groups.

Associations between time-weighted postnatal methylmercury exposure from fish consumption and neurodevelopmental outcomes through 24 years of age in the Seychelles Child Development Study Main Cohort

PurposeMethylmercury (MeHg) is a known neurodevelopmental toxicant in sufficient dosage and is universally found in fish. Current fish advisories for children are based on epidemiology studies examining prenatal exposure with a premise that MeHg exposure resulting from children eating fish could also be neurotoxic and have long-term consequences. However, the evidence that this assumption is true is limited. We investigated postnatal MeHg exposure from regular fish consumption using time weighted Hg measurements to determine if there are neurotoxic consequences. MethodsWe examined 85 neurodevelopmental outcomes measured from ages 9–24 years in the Seychelles Child Development Study Main Cohort (n = 312–550) and examined their association with time-weighted measures of postnatal MeHg exposure in childhood and early adulthood. Postnatal MeHg exposure measured in the first cm of participants’ hair samples collected at seven evaluations were used to create two time-weighted (TW) average MeHg exposure metrics, one for childhood (TW-C) and the other for early adulthood (TW-A). TW-C was based on Hg measures at three ages between 6 months and 5.5 years, and TW-A was based on Hg measured at up to four ages between 17 and 24 years. We examined the association between each of these exposure metrics and the neurodevelopmental outcomes using linear regression with adjustment for covariates known to influence neurodevelopmental outcomes. ResultsThere were 14 statistically significant associations between a postnatal metric and an endpoint. Six were associated with the TW-C and eight with the TW-A. Thirteen were adverse. Only the TW-C association at 9 years with the Bender Gestalt error score showed improvement. TW-C was adversely associated at 9 years with the Continuous Performance Task risk score, at 22 years with the Boston Naming Test (BNT) total and no cues scores, and at 24 years with the Test of Variables of Attention (TOVA) auditory response time variability and visual response time mean on the logarithmic scale. TW-A was adversely associated at 17 years with the Wisconsin Card Sorting Test % total errors, the Woodcock-Johnson passage comprehension, and the CANTAB rapid visual information processing false alarms, and at 22 years with the BNT total and no cue scores, the CANTAB rapid visual information processing false alarms and the intra-extra dimensional shift total errors and trials. ConclusionThese findings suggest that postnatal MeHg exposure may be adversely associated with neurodevelopmental outcomes in early adulthood. However, the associations are statistical and of unknown, if any, clinical significance. The results need confirmation in other cohorts.

Molecular Fates of Organometallic Mercury in Human Brain.

Mercury is ubiquitous in the environment, with rising levels due to pollution and climate change being a current global concern. Many mercury compounds are notorious for their toxicity, with the potential of organometallic mercury compounds for devastating effects on the structures and functions of the central nervous system being of particular concern. Chronic exposure of human populations to low levels of methylmercury compounds occurs through consumption of fish and other seafood, although the health consequences, if any, from this exposure remain controversial. We have used high energy resolution fluorescence detected X-ray absorption spectroscopy to determine the speciation of mercury and selenium in human brain tissue. We show that the molecular fate of mercury differs dramatically between individuals who suffered acute organometallic mercury exposure (poisoning) and individuals with chronic low-level exposure from a diet rich in marine fish. For long-term low-level methylmercury exposure from fish consumption, mercury speciation in brain tissue shows methylmercury coordinated to an aliphatic thiolate, resembling the coordination environment observed in marine fish. In marked contrast, for short-term high-level exposure, we observe the presence of biologically less available mercuric selenide deposits, confirmed by X-ray fluorescence imaging, as well as mercury(II)-bis-thiolate complexes, which may be signatures of severe poisoning in humans. These differences between low-level and high-level exposures challenge the relevance of studies involving acute exposure as a proxy for low-level chronic exposure.

Protective function of the SQSTM1/p62-NEDD4 complex against methylmercury toxicity

SQSTM1/p62, hereinafter referred to as p62, is a stress-induced cellular protein that interacts with various signaling proteins as well as ubiquitinated proteins to regulate a variety of cellular functions and cell survival. Methylmercury (MeHg) exposure increases the levels of p62, the latter playing a protective role in MeHg-induced toxicity. However, the underlying mechanism by which p62 alleviates MeHg toxicity remains poorly understood. Herein, we report the interaction of p62 with neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), a HECT E3 ubiquitin ligase. The region of p62 where NEDD4 binds is located at the proline- and arginine (PR)-rich region (amino acids: 102–119), C-terminal extension of the Phox and Bem1 (PB1) domain. To evaluate the importance of the p62-NEDD4 complex, we examined the compensation of deletion mutant (GFP-Δ102-119 p62) for the lack of endogenous p62 in MEFs. GFP-p62/p62KO cells exhibited significantly higher cell viability than GFP-Δ102-119 p62/p62KO cells after treatment with MeHg. Our findings suggest novel mechanisms to alleviate MeHg toxicity through p62-NEDD4 complex formation.

Analysis of the risk of exposure to methyl-mercury due to non intentional consumption of shark meat in males of Mexico city’s metropolitan area

In this paper we estimate the probability and risk coefficient of methyl mercury exposure due to unintentional consumption of shark meat for the male inhabitants of Mexico City's metropolitan area. Using statistical and numerical methods, we built a risk function in terms of the concentration and life stage variables. Using mathematical results from the singularity theory, dynamical systems and differential geometry, we obtained that both, the risk average (2.96) and the risk probability (85%) are high. We also obtained the critical ages or risk which are 5.1 years for boys and 87 years for senior men, but this will be relevant only to those men who reach this age. All this, means that in the analysed sample, there is a high probability of developing deleterious health effects. So, if men want to consume fish products, they must buy whole fish to avoid the replacement

Differentiated emission control strategy based on comprehensive evaluation of multi-media pollution: Case of mercury emission control

In order to comprehensively evaluate the environmental impact of multi-media mercury pollution under differentiated emission control strategies in China, a literature review and case studies were carried out. Increased human exposure to methylmercury was assessed through the dietary intake of residents in areas surrounding a typical coal-fired power plant and a zinc (Zn) smelter, located either on acid soil with paddy growth in southern China, or on alkaline soil with wheat growth in northern China. Combined with knowledge on speciated mercury in flue gas and the fate of mercury in the wastewater or solid waste of the typical emitters applying different air pollution control devices, a simplified model was developed by estimating the incremental daily intake of methylmercury from both local and global pollution. Results indicated that air pollution control for coal-fired power plants and Zn smelters can greatly reduce health risks from mercury pollution, mainly through a reduction in global methylmercury exposure, but could unfortunately induce local methylmercury exposure by transferring more mercury from flue gas to wastewater or solid waste, then contaminating surrounding soil, and thus increasing dietary intake via crops. Therefore, tightening air emission control is conducive to reducing the comprehensive health risk, while the environmental equity between local and global pollution control should be fully considered. Rice in the south tends to have higher bioconcentration factors than wheat in the north, implying the great importance of strengthening local pollution control in the south, especially for Zn smelters with higher contribution to local pollution.