Methylmercury Induces Apoptosis in Mouse C17.2 Neural Stem Cells through the Induction of OSGIN1 Expression by NRF2.

Methylmercury is a known environmental pollutant that exhibits severe neurotoxic effects. However, the mechanism by which methylmercury causes neurotoxicity remains unclear. To date, we have found that oxidative stress-induced growth inhibitor 1 (OSGIN1), which is induced by oxidative stress and DNA damage, is also induced by methylmercury. Therefore, in this study, we investigated the relationship between methylmercury toxicity and the induction of OSGIN1 expression using C17.2 cells, which are mouse brain neural stem cells. Methylmercury increased both OSGIN1 mRNA and protein levels in a time- and concentration-dependent manner. Moreover, these increases were almost entirely canceled out by pretreatment with actinomycin D, a transcription inhibitor. Furthermore, similar results were obtained from cells in which expression of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) was suppressed, indicating that methylmercury induces OSGIN1 expression via NRF2. Methylmercury causes neuronal cell death by inducing apoptosis. Therefore, we next investigated the role of OSGIN1 in methylmercury-induced neuronal cell death using the activation of caspase-3, which is involved in apoptosis induction, as an indicator. As a result, the increase in cleaved caspase-3 (activated form) induced by methylmercury exposure was decreased by suppressing OSGIN1, and the overexpression of OSGIN1 further promoted the increase in cleaved caspase-3 caused by methylmercury. These results suggest, for the first time, that OSGIN1 is a novel factor involved in methylmercury toxicity, and methylmercury induces apoptosis in C17.2 cells through the induction of OSGIN1 expression by NRF2.

Coastal Mussel (Mytilus spp.) Soft Tissues as Bioindicators of Methylmercury: Exploring the Relationship Between Condition Index and Methylmercury Concentrations.

We investigated total mercury (THg) and methylmercury (MeHg) concentrations in coastal mussels (Mytilus spp.) sampled from the Minas Basin, Bay of Fundy and evaluated the relationship with condition index (CI). THg concentrations were low in sediment (mean THg = 5.15 ± 2.11 ng/g dw; n = 6) and soft tissues (mean THg = 62.3 ± 13.7 ng/g; mean MeHg = 13.2 ± 6.3 ng/g; n = 57). The THg in tissues had no significant relationship with CI (Rs= -0.205, p = 0.126). MeHg in tissues were significantly and negatively correlated with condition index (Rs = -0.361, p = 0.006) indicating that healthier mussels (higher CI) have lower mercury content possibly due to elimination strategies or growth dilution.

Predictive modeling of methylmercury in rice (Oryza sativa L.) and species-sensitivity-distribution-based derivation of the threshold of soil mercury in karst mountain areas.

The bioavailable mercury (Hg) in the soil is highly active and can affect the formulation of methyl-Hg (MeHg) in soil and its accumulation in rice. Herein, we predicted the concentration of MeHg in rice using bioavailable Hg extracted from soils; additionally, we determined the threshold value of soil Hg in karst mountain areas based on species sensitivity distribution. The bioavailable Hg was extracted using calcium chloride, hydrochloric acid (HCl), diethylenetriaminepentaacetic acid mixture, ammonium acetate, and thioglycolic acid. Results showed that HCl is the best extractant, and the prediction model demonstrated good predictability of the MeHg concentration in rice based on the HCl-extractable Hg, pH, and soil organic matter (SOM) data. Compared with the actual MeHg concentration in rice, approximately 99% of the predicted values (n = 103) were within the 95% prediction range, indicating the good performance of the rice MeHg prediction model based on soil pH, SOM, and bioavailable Hg in karst mountain areas. Based on this MeHg prediction model, the safety threshold of soil Hg was calculated to be 0.0936 mg/kg, which is much lower than the soil pollution risk screening value of agricultural land (0.5 mg/kg), suggesting that a stricter standard should be applied regarding soil Hg in karst mountain areas. This study presents the threshold of soil Hg pollution for rice safety in karst mountain areas, and future studies should target this threshold range.

Application of diffusive gradient in thin films probes to monitor trace levels of labile methylmercury in freshwaters.

This study aimed to optimize the methods for sampling and analyzing methylmercury (MeHg) concentrated within diffusive gradients in thin films (DGT) and its application to different water bodies. We explored the elution solution for MeHg, comprised of 1.13 mM thiourea and 0.1M HCl, optimizing its volume to 50 mL. In addition, we found that it is necessary to analyze the entire extraction solution after adjusting its pH, to ensure completion of the ethylation reaction. The DGT samplers were deployed in two distinct aquatic environments (i.e., Okjeong Lake and Nakdong River) for up to 6 weeks, and this study demonstrated to predict the time-weighted average concentration with a diffusion coefficient of 7.65 × 10-6 cm2 s-1 for MeHg in the diffusive gel. To assess the diffusive boundary layer (DBL) effects, the DGT samplers with different agarose diffusive gel thickness were deployed. The mass of MeHg accumulated in the DGT resin at a given time decreased with increasing diffusive gel thickness, because of creating longer diffusion pathways within thicker gels. The labile MeHg concentration estimated by the DGT in Okjeong Lake and Nakdong River are found in the range of 61-111 and 55-105 pg L-1, respectively, which were found to be similar to the grab sampling data. Additionally, this study evaluated depth-dependent MeHg in Okjeong Lake. The vertical profile results showed that the concentration of MeHg at the depth of 2.3 and 15.7 m are about 1.5 and 4.6 times of the DGT installed at 0.3 m of the surface layer, respectively, suggesting potential mercury methylation in deep waters. These findings have practical implications for predicting bioavailability, assessing risks, and formulating strategies for water body management and contamination remediation.

New Insights into MeHg Accumulation in Rice (Oryza sativa L.): Evidence from Cysteine.

The intake of methylmercury (MeHg)-contaminated rice poses immense health risks to rice consumers. However, the mechanisms of MeHg accumulation in rice plants are not entirely understood. The knowledge that the MeHg-Cysteine complex was dominant in polished rice proposed a hypothesis of co-transportation of MeHg and cysteine inside rice plants. This study was therefore designed to explore the MeHg accumulation processes in rice plants by investigating biogeochemical associations between MeHg and amino acids. Rice plants and underlying soils were collected from different Hg-contaminated sites in the Wanshan Hg mining area. The concentrations of both MeHg and cysteine in polished rice were higher than those in other rice tissues. A significant positive correlation between MeHg and cysteine in rice plants was found, especially in polished rice, indicating a close geochemical association between cysteine and MeHg. The translocation factor (TF) of cysteine showed behavior similar to that of the TF of MeHg, demonstrating that these two chemical species might share a similar transportation mechanism in rice plants. The accumulation of MeHg in rice plants may vary due to differences in the molar ratios of MeHg to cysteine and the presence of specific amino acid transporters. Our results suggest that cysteine plays a vital role in MeHg accumulation and transportation inside rice plants.

Unveiling the Sources and Transfer of Mercury in Forest Bird Food Chains Using Techniques of Vivo-Nest Video Recording and Stable Isotopes.

Knowledge gaps in mercury (Hg) biomagnification in forest birds, especially in the most species-rich tropical and subtropical forests, limit our understanding of the ecological risks of Hg deposition to forest birds. This study aimed to quantify Hg bioaccumulation and transfer in the food chains of forest birds in a subtropical montane forest using a bird diet recorded by video and stable Hg isotope signals of biological and environmental samples. Results show that inorganic mercury (IHg) does not biomagnify along food chains, whereas methylmercury (MeHg) has trophic magnification factors of 7.4-8.1 for the basal resource-invertebrate-bird food chain. The video observations and MeHg mass balance model suggest that Niltava (Niltava sundara) nestlings ingest 78% of their MeHg from forest floor invertebrates, while Flycatcher (Eumyias thalassinus) nestlings ingest 59% from emergent aquatic invertebrates (which fly onto the canopy) and 40% from canopy invertebrates. The diet of Niltava nestlings contains 40% more MeHg than that of Flycatcher nestlings, resulting in a 60% higher MeHg concentration in their feather. Hg isotopic model shows that atmospheric Hg0 is the main Hg source in the forest bird food chains and contributes >68% in most organisms. However, three categories of canopy invertebrates receive ∼50% Hg from atmospheric Hg2+. Overall, we highlight the ecological risk of MeHg exposure for understory insectivorous birds caused by atmospheric Hg0 deposition and methylation on the forest floor.

Human health risk assessment based on a total diet study of daily mercury intake in Chengdu, China.

To assess the total daily mercury intake and main exposure sources of residents, six food groups, including marine fish, freshwater fish, poultry, livestock, vegetables, and cereals, were collected from five districts of Chengdu, China. The median concentrations of total mercury (THg) and methylmercury (MeHg) were 12.8 and 6.94 µg kg-1 ww, respectively. Cereals (32.2%), vegetables (30.5%), and livestock (16.2%) contributed to a much larger extent to the total consumption for the participants in Chengdu. All food categories that contributed the most of THg (2.16 µg day-1) and MeHg 1.44 (µg day-1) to the daily intake in Chengdu were cereals and marine fish, respectively. The total Hazard Ratios values below 1 in this study indicate that there is no health risk associated with Hg ingestion from the consumption of these foods for the residents in Chengdu.

Suppression of mercury methylation in soil and methylmercury accumulation in rice by dissolved organic matter derived from sulfur-rich rape straw.

Straw amendment significantly enhances mercury (Hg) methylation and subsequent methylmercury (MeHg) bioaccumulation in Hg-contaminated paddy fields by releasing dissolved organic matter (DOM). This study comprehensively investigates the regulatory mechanisms of DOM and its different molecular weights derived from sulfur-rich rape straw (RaDOM) and composted rape straw (CRaDOM) applied in the rice-filling stage on soil MeHg production and subsequent bioaccumulation in rice grains. The results indicated that the amendment of RaDOM and CRaDOM significantly reduced soil MeHg content by 42.40-62.42%. This reduction can be attributed to several factors, including the suppression of Hg-methylating bacteria in soil, the supply of sulfate from RaDOM and CRaDOM, and the increase in the humification, molecular weight, and humic-like fractions of soil DOM. Additionally, adding RaDOM increased the MeHg bioaccumulation factor in roots by 27.55% while inhibiting MeHg transportation by 12.24% and ultimately reducing MeHg content in grains by 21.24% compared to the control group. Similarly, CRaDOM enhanced MeHg accumulation by 25.19%, suppressed MeHg transportation by 39.65%, and reduced MeHg levels in the grains by 27.94%. The assimilation of sulfate derived from RaDOM and CRaDOM into glutathione may be responsible for the increased retention of MeHg in the roots. Over the three days, there was a significant decrease in soil MeHg content as the molecular weight of RaDOM increased; conversely, altering the molecular weight of CRaDOM demonstrated an inverse trend. However, this pattern was not observed after 12 days. Applying sulfur-rich rape DOM can help mitigate MeHg accumulation in paddy fields by regulating the quality of soil DOM, sulfur cycling, and Hg-methylating bacteria.

The mystery of methylmercury-perturbed calcium homeostasis: AMPK-DRP1-dependent mitochondrial fission initiates ER-mitochondria contact formation.

Methylmercury (MeHg), as a global environmental pollutant, is of concern globally due to its neurodevelopmental toxicity. Mitochondria-associated membranes (MAMs) are highly dynamic sites of endoplasmic reticulum (ER)-haemocyte contact. MAMs are closely associated with the pathophysiology of neurological disorders due to their role in the transfer of calcium ions (Ca2+) between mitochondria and the ER. However, the molecular mechanisms that control these interactions in MeHg-induced neurotoxicity have not yet been characterized. In the current study, MeHg caused increases in the levels of both cytosolic and mitochondrial Ca2+ in PC12 cells and promoted MAMs formation in both in vivo and in vitro experiments. Of note, MeHg perturbed mitochondrial dynamics, promoting a shift toward a fission phenotype, and this was supported by the dysregulation of fission regulators. Interestingly, the MeHg-induced promotion of MAMs formation and increase in Ca2+ levels were effectively attenuated by the inhibition of mitochondrial fission using Mdivi-1, a DRP1 inhibitor. Furthermore, MeHg triggered the AMPK pathway, and most of the aforementioned changes were significantly rescued by Compound C. Mechanistic investigations revealed a reciprocal relationship between AMPK- and Ca2+-mediated mitochondrial fission. The specific inhibitor of Ca2+ uniporter, ruthenium-red (RuR), effectively abolished the feedback regulation of mitochondrial dynamics and MAMs formation mediated by AMPK in response to MeHg-induced Ca2+ overload. This study reveals a novel role of AMPK-DRP1-mediated mitochondrial fragmentation in the coupling of ER-mitochondrial calcium microdomains in MeHg-induced neurotoxicity. The findings provide valuable insights for the development of strategies to regulate mitochondrial imbalances in neurological diseases.

A Comparative Study of Mercury Bioaccumulation in Bivalve Molluscs from a Shallow Estuarine Embayment.

In estuarine food webs, bivalve molluscs transfer nutrients and pollutants to higher trophic levels. Mercury (Hg) pollution is ubiquitous, but it is especially elevated in estuaries historically impacted by industrial activities, such as those in the U.S. Northeast. Monomethylmercury (MeHg), the organic form of Hg, is highly bioaccumulative and transferable in the food web resulting in the highest concentrations in the largest and oldest marine predators. Patterns of Hg concentrations in marine bivalve molluscs, however, are poorly understood. In this study, inorganic Hg (iHg), MeHg, and the total Hg (THg) in soft tissues of the northern quahogs (Mercenaria mercenaria), eastern oysters (Crassostrea virginica), and ribbed mussels (Geukensia demissa) from eastern Long Island sound, a temperate estuary of the western North Atlantic Ocean was investigated. In all three species, concentrations of THg remained similar between the four sampling months (May, June, July, and September), and were mostly independent of animal size. In quahogs, MeHg and iHg displayed significant (p < 0.05) positive (iHg in May and June) and negative (MeHg in July and September) changes with shell height. Variability in concentrations of THg, MeHg, and iHg, both inter- and intra-specifically was high and greater in quahogs and oysters (THg: 37, 39%, MeHg: 28, 39%, respectively) than in mussels (THg: 13%, MeHg: 20%). The percentage of THg that was MeHg (%MeHg) was also highly variable in the three species (range: 10-80%), highlighting the importance of measuring MeHg and not only THg in molluscs.

Characterizing the risk related to the exposure to methylmercury over a lifetime: A global approach using population internal exposure.

Seafood products accumulate methylmercury throughout the food chain and are the main source of methylmercury exposure. Methylmercury may trigger a number of adverse health effects, such as neurodevelopmental or nephrotoxic effects, the risk of which cannot be ruled out for the French high consumers of seafood. The characterisation of methylmercury-related risks is generally based on short-term dietary exposure without considering changes in consumption and exposure over the lifetime. Additionally, focusing on short-term dietary exposure, the fate of methylmercury (especially its accumulation) in the organism is not considered. The present study proposes a methodology basing risk characterization on estimates of body burden over a lifetime. First, trajectories of dietary exposures throughout lifetime were constructed based on the actual concentrations of total diet studies for a fictive representative French population, taking into account the social, economic and demographic parameters of individuals. Next, the fate of methylmercury in the body was estimated, based on these trajectories, using a specific physiologically-based kinetic (PBK) model that generated a representative pool of body burden trajectories. Simulated hair mercury concentrations were closed to previously reported French representative human biomonitoring data. Results showed that at certain stages of life, concentrations of methylmercury in hair were higher than the human biomonitoring guidance value set at 2.5 µg/g of hair by JECFA. This study showed the added value, in the case of substances accumulating in the body, of estimating dietary exposure over a lifetime and using exposure biomarkers estimated by a PBK model characterize the risk.

The acute neurotoxicity of inorganic mercury in Mactra chinensis philippi.

Inorganic mercury (IHg) is hazardous to marine organisms especially resulting in neurotoxicity, bivalves are sensitive to pollutants as "ocean sentinel", but data on the neurotoxicity of IHg in bivalves are sparse. So we chosed M. chinensis philippi with typical neural structures in bivalves to investigate the neurotoxicity of IHg, which could be helpful to understand the specificity of neural regulation and the response characteristics of bivalves. After acute exposed to IHg (HgCl2) for 24 h, the metabolites of ganglion tissues in M. chinensis philippi were evaluated using 1H-nuclear magnetic resonance based metabolomics; Ca2+, neurotransmitters (nitric oxide, glutamate, acetylcholine) and related enzymes (calcineurin, nitric oxide synthase and acetylcholinesterase) were measured using biochemical detection. Compared to the control group, the levels of the nitric oxide (81.04 ± 12.84 µmol/g prot) and acetylcholine (30.93 ± 12.57 µg/mg prot) in M. chinensis philippi of IHg-treated were decreased, while glutamate (2.11 ± 0.61 mmol/L) increased significantly; the activity of nitric oxide synthase (679.34 ± 135.33 U/mg prot) was increased, while acetylcholinesterase (1.39 ± 0.44 U/mg prot) decreased significantly, and the activity of calcineurin (0.52 ± 0.02 U/mg prot) had a statistically insignificant increasing tendency. The concentration of Ca2+ (0.92 ± 0.46 mmol/g prot) in the IHg-treated group was significantly higher than that in the control group. OPLS-DA was performed to reveal the difference in metabolites between the control and IHg-challenged groups, the metabolites of glucose, glutamine, inosine, succinate, glutamate, homarine, and alanine were sensitive to IHg, subsequently metabolic pathways that were affected including glucose metabolism, glutamine metabolism, nucleotide metabolism, Krebs cycle, amino acid metabolism and osmotic regulation. In our study, IHg interfered with metabolites in M. chinensis philippi, thus the corresponding metabolic pathways were changed, which influenced the neurotransmitters subsequently. Furthermore, Ca2+overload affected the synthesis or degradation of the neurotransmitters, and then the altered neurotransmitters involved in changes in metabolic pathways again. Overall, we hypothesized that the neurotoxic effects of IHg on bivalve were in close contact with metabolism, neurotransmitters, related enzymes and Ca2+, which could be effective neurotoxic biomarkers for marine environmental quality assessment, and also provide effective data for the study of the regulatory mechanism of the nervous system in response to IHg in bivalves.

Sea anemones, methylmercury, and bacterial infection: A closer look at multiple stressors.

Specimens of the Mediterranean sea anemone Anemonia viridis were exposed to methylmercury (MeHg) and bacterial infection to study their immune responses to a well-known toxic pollutant. Anemones were housed in laboratory conditions and divided into five experimental groups: 1. control (no microinjection); 2. filtered seawater + buffer injection; 3. filtered seawater + Escherichia coli injection; 4. MeHg + buffer injection; 5. MeHg + E. coli injection. Data showed an increase in antioxidant enzyme production compared to the constitutive condition, while methylmercury inhibited lysozyme production. The buffer inoculation had no statistically significant effects on the animals. In addition, electrophoretic and protease analyses revealed differences in the type of proteins produced, as well as a modulation of proteases depending on the treatment. The study demonstrated the immunomodulatory effect of the organic pollutant on A. viridis, validating its use as a model organism for marine coastal biomonitoring programmes and multiple stress studies.

Genomic and transcriptomic characterization of methylmercury detoxification in a deep ocean Alteromonas mediterranea ISS312.

Methylmercury (MeHg) is one of the most worrisome pollutants in marine systems. MeHg detoxification is mediated by merB and merA genes, responsible for the demethylation of MeHg and the reduction of inorganic mercury, respectively. Little is known about the biological capacity to detoxify this compound in marine environments, and even less the bacterial transcriptional changes during MeHg detoxification. This study provides the genomic and transcriptomic characterization of the deep ocean bacteria Alteromonas mediterranea ISS312 with capacity for MeHg degradation. Its genome sequence revealed four mer operons containing three merA gene and two merB gene copies, that could be horizontally transferred among distant related genomes by mobile genetic elements. The transcriptomic profiling in the presence of 5 µM MeHg showed that merA and merB genes are within the most expressed genes, although not all mer genes were equally transcribed. Besides, we aimed to identify functional orthologous genes that displayed expression profiles highly similar or identical to those genes within the mer operons, which could indicate they are under the same regulatory controls. We found contrasting expression profiles for each mer operon that were positively correlated with a wide array of functions mostly related to amino acid metabolism, but also to flagellar assembly or two component systems. Also, this study highlights that all merAB genes of the four operons were globally distributed across oceans layers with higher transcriptional activity in the mesopelagic deeper waters. Our study provides new insights about the transcriptional patterns related to the capacity of marine bacteria to detoxify MeHg, with important implications for the understanding of this process in marine ecosystems.

Soil organic matter degradation and methylmercury dynamics in Hg-contaminated soils: Relationships and driving factors.

Biodegradation of soil organic matter (SOM), which involves greenhouse gas (GHG) emissions, plays an essential role in the global carbon cycle. Over the past few decades, this has become an important research focus, particularly in natural ecosystems. SOM biodegradation significantly affects contaminants in the environment, such as mercury (Hg) methylation, producing highly toxic methylmercury (MeHg). However, the potential link between GHG production from SOM turnover in contaminated soils and biogeochemical processes involving contaminants remains unclear. In this study, we investigated the dynamics of GHG, MeHg production, and the relationship between biogeochemical processes in soils from two typical Hg mining sites. The two contaminated soils have different pathways, explaining the significant variations in GHG and MeHg production. The divergence of the microbial communities in these two biogeochemical processes is essential. In addition to the microbial role, abiotic factors such as Hg species can significantly affect MeHg production. On the other hand, we found an inverse relationship between CH4 and MeHg, suggesting that carbon emission reduction policies and management could inadvertently increase the MeHg levels. This highlights the need for an eclectic approach to organic carbon sequestration and contaminant containment. These findings suggest that it is difficult to establish a general pattern to describe and explain the SOM degradation and MeHg production in contaminated soils within the specific scenarios. However, this study provides a case study and helpful insights for further understanding the links between environmental risks and carbon turnover in Hg mining areas.

Non-mercury methylating microbial taxa are integral to understanding links between mercury methylation and elemental cycles in marine and freshwater sediments.

The goal of this study was to explore the role of non-mercury (Hg) methylating taxa in mercury methylation and to identify potential links between elemental cycles and Hg methylation. Statistical approaches were utilized to investigate the microbial community and biochemical functions in relation to methylmercury (MeHg) concentrations in marine and freshwater sediments. Sediments were collected from the methylation zone (top 15 cm) in four Hg-contaminated sites. Both abiotic (e.g., sulfate, sulfide, iron, salinity, total organic matter, etc.) and biotic factors (e.g., hgcA, abundances of methylating and non-methylating taxa) were quantified. Random forest and stepwise regression were performed to assess whether non-methylating taxa were significantly associated with MeHg concentration. Co-occurrence and functional network analyses were constructed to explore associations between taxa by examining microbial community structure, composition, and biochemical functions across sites. Regression analysis showed that approximately 80% of the variability in sediment MeHg concentration was predicted by total mercury concentration, the abundances of Hg methylating taxa, and the abundances of the non-Hg methylating taxa. The co-occurrence networks identified Paludibacteraceae and Syntrophorhabdaceae as keystone non Hg methylating taxa in multiple sites, indicating the potential for syntrophic interactions with Hg methylators. Strong associations were also observed between methanogens and sulfate-reducing bacteria, which were likely symbiotic associations. The functional network results suggested that non-Hg methylating taxa play important roles in sulfur respiration, nitrogen respiration, and the carbon metabolism-related functions methylotrophy, methanotrophy, and chemoheterotrophy. Interestingly, keystone functions varied by site and did not involve carbon- and sulfur-related functions only. Our findings highlight associations between methylating and non-methylating taxa and sulfur, carbon, and nitrogen cycles in sediment methylation zones, with implications for predicting and understanding the impact of climate and land/sea use changes on Hg methylation.

Significant biomagnification of methylmercury in songbird nestlings through a rice-based food web: Insights from stable mercury isotopes.

To elucidate the sources and transfer of mercury (Hg) in terrestrial food chains, particularly in heavily Hg-contaminated rice paddy ecosystems, we collected rice leaves, invertebrates, and Russet Sparrow nestlings from a clear food chain and analyzed the dietary compositions and potential Hg sources using stable Hg isotopes coupled with a Bayesian isotope mixing model (BIMM). Our findings indicated that MeHg exposure is dominant through the dietary route, with caterpillars, grasshoppers, and katydids being the main prey items, while the less provisioned spiders, dragonflies, and mantises contributed the most of the Hg to nestlings. We found minimal MIF but certain MDF in this terrestrial food chain and identified two distinct MeHg sources of dietary exposure and maternal transfer. We firstly found that the dietary route contributed substantially (almost tenfold) more MeHg to the nestlings than maternal transfer. These findings offer new insights into the integration of Hg from the dietary route and maternal transfers, enhancing our understanding of fluctuating Hg exposure risk during the nestling stage. Our study suggested that Hg isotopes combined with BIMM is an effective approach for tracing Hg sources in birds and for gaining in-depth insight into the trophic transfers and biomagnification of MeHg in food chains.

Adherence to the EAT-Lancet diet in relation to mortality and exposure to food contaminants in population-based cohorts of Swedish men and women.

BACKGROUND: The EAT-Lancet diet was created to support dietary transition towards sustainable diets. Current evidence indicates that adherence to the EAT-Lancet diet may reduce mortality risk, yet how adherence may impact dietary exposure to food contaminants remains unexplored. We aimed to estimate the association between adherence to the EAT-Lancet diet and i) all-cause, cardiovascular-, and cancer-mortality and ii) predicted dietary exposure to the following food contaminants: cadmium, methylmercury, polychlorinated biphenyls (PCBs), and pesticide residues. METHODS: We used self-reported dietary data from a 96-item food frequency questionnaire of two population-based cohorts - the Cohort of Swedish Men (n = 35,687) and the Swedish Mammography Cohort (n = 32,488). The EAT-Lancet Adherence Index (EAI) was created by scoring consumption of the 14 dietary components included in the EAT-Lancet diet (totalling 0-14 points). Cox proportional hazards regression models were applied to assess the association between EAI and mortality outcomes, presented as multivariable-adjusted hazard ratios (HR) and 95 % confidence intervals (CI). Descriptive statistics were used to characterise predicted exposure to food contaminants, and the correlations between EAI and food contaminants assessed using Spearman's rank correlation. RESULTS: Increased adherence to the EAT-Lancet diet was associated with a lower risk of all-cause mortality (per 3-point increase in EAI: HR = 0.93; CI:0.90,0.97 and HR = 0.91; CI:0.87,0.95 for men and women, respectively) and cardiovascular-mortality (corresponding HR = 0.94; CI:0.88,1.00 and HR = 0.93; CI:0.87,1.00). No clear association was found with cancer-mortality. Increasing EAI was correlated with increased predicted dietary exposure to cadmium, methylmercury, PCBs, and pesticide residues and their median predicted dietary exposures were greater in the high adherence group, compared to the low adherence group. CONCLUSION: High adherence to the EAT-Lancet diet is associated with a reduction in risk of all-cause and cardiovascular-mortality, but also increased dietary exposure to food contaminants.

BDNF specifically expressed in hippocampal neurons is involved in methylmercury neurotoxicity resistance.

Methylmercury (MeHg) causes selective neuronal damage to cerebrocortical neurons (CCNs) in the central nervous system, but not to hippocampal neurons (HiNs), which are highly vulnerable to neurodegenerative diseases. In our previous study using cultured rat neurons, we performed a comprehensive gene expression analysis and found that the brain-derived neurotrophic factor (BDNF), a neurotrophin (NT), was specifically expressed in HiNs. Therefore, to elucidate the causal factors of MeHg toxicity resistance in HiNs, we conducted a comparative study of the protein expression and function of several NTs, including BDNF, using CCNs showing vulnerability to MeHg toxicity and HiNs showing resistance. BDNF was specifically expressed in HiNs, whereas nerve growth factor was barely detectable in either neuron type. In addition, other NTs, NT3 and NT4/5, were expressed in small but nearly equal amounts in both neuron types. Furthermore, among the various pathways involved in MeHg neurotoxicity, the p44/42 MAPK pathway was specifically activated in HiNs, even without MeHg treatment. siRNAs were used to reduce NTs in both neuron types. Only a specific reduction in BDNF attenuated the resistance to MeHg toxicity and p44/42 MAPK activation in HiNs. In addition, the external addition of BDNF and NT4/5, which act on the same tyrosine receptor kinase (Trk), TrkB, suppressed MeHg neurotoxicity in both neuron types. These results suggest that BDNF, expressed specifically in HiNs, is involved in the resistance to MeHg neurotoxicity via TrkB. Additionally, the activation of the p44/42 MAPK pathway may contribute to the inhibitory effect of BDNF on MeHg neurotoxicity.

Characterization of pathological changes in the olfactory system of mice exposed to methylmercury.

Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients.