The origin of methyl group in methanogen-mediated mercury methylation: From the Wolfe cycle.

Methylmercury (MeHg) is a bioaccumulating neurotoxin mainly produced by anaerobic microorganisms, with methanogen being one of the important methylators. A critical aspect for understanding the mechanism for microbial mercury (Hg) methylation is the origin of the methyl group. However, the origin of methyl group in methanogen-mediated Hg methylation remains unclear. This study aims to identify the source of methyl group for MeHg synthesis in methanogens. Our study revealed that Hg methylation in Methanospirillum hungatei JF-1 is closely related to methanogenesis process, according to the results of proteomic study and substrate limitation study. Next, we proved that nearly all methyl group in MeHg derives from the Wolfe cycle in this species, rather than the previously demonstrated acetyl-coenzyme A pathway, based on the results of 13C labeling study. We then proposed the Wolfe cycle-dependent Hg methylation mechanism in this species. Further genome analyses and 13C labeling experiments indicated that the involvement of the Wolfe cycle in Hg methylation is probably a universal feature among Hg-methylating methanogens. These findings reveal a unique Hg methylation mechanism in methanogens. Our study broadens the carbon substrates and controlling factors for MeHg synthesis in the environment, which can inform the prediction of MeHg production potential and remediation strategies for MeHg contamination.

Climate-driven changes of global marine mercury cycles in 2100.

Human exposure to monomethylmercury (CH3Hg), a potent neurotoxin, is principally through the consumption of seafood. The formation of CH3Hg and its bioaccumulation in marine food webs experience ongoing impacts of global climate warming and ocean biogeochemistry alterations. Employing a series of sensitivity experiments, here we explicitly consider the effects of climate change on marine mercury (Hg) cycling within a global ocean model in the hypothesized twenty-first century under the business-as-usual scenario. Even though the overall prediction is subjected to significant uncertainty, we identify several important climate change impact pathways. Elevated seawater temperature exacerbates elemental Hg (Hg0) evasion, while decreased surface wind speed reduces air-sea exchange rates. The reduced export of particulate organic carbon shrinks the pool of potentially bioavailable divalent Hg (HgII) that can be methylated in the subsurface ocean, where shallower remineralization depth associated with lower productivity causes impairment of methylation activity. We also simulate an increase in CH3Hg photodemethylation potential caused by increased incident shortwave radiation and less attenuation by decreased sea ice and chlorophyll. The model suggests that these impacts can also be propagated to the CH3Hg concentration in the base of the marine food web. Our results offer insight into synergisms/antagonisms in the marine Hg cycling among different climate change stressors.

Evidence that Pacific tuna mercury levels are driven by marine methylmercury production and anthropogenic inputs.

Pacific Ocean tuna is among the most-consumed seafood products but contains relatively high levels of the neurotoxin methylmercury. Limited observations suggest tuna mercury levels vary in space and time, yet the drivers are not well understood. Here, we map mercury concentrations in skipjack tuna across the Pacific Ocean and build generalized additive models to quantify the anthropogenic, ecological, and biogeochemical drivers. Skipjack mercury levels display a fivefold spatial gradient, with maximum concentrations in the northwest near Asia, intermediate values in the east, and the lowest levels in the west, southwest, and central Pacific. Large spatial differences can be explained by the depth of the seawater methylmercury peak near low-oxygen zones, leading to enhanced tuna mercury concentrations in regions where oxygen depletion is shallow. Despite this natural biogeochemical control, the mercury hotspot in tuna caught near Asia is explained by elevated atmospheric mercury concentrations and/or mercury river inputs to the coastal shelf. While we cannot ignore the legacy mercury contribution from other regions to the Pacific Ocean (e.g., North America and Europe), our results suggest that recent anthropogenic mercury release, which is currently largest in Asia, contributes directly to present-day human mercury exposure.

Prefrontal cortical network dysfunction from acute neurotoxicant exposure.

Prefrontal cortical (PFC) dysfunction has been linked to disorders exhibiting deficits in cognitive performance, attention, motivation, and impulse control. Neurons of the PFC are susceptible to glutamatergic excitotoxicity, an effect associated with cortical degeneration in frontotemporal disorders (FTDs). PFC susceptibility to environmental toxicant exposure, one possible contributor to sporadic FTD, has not been systematically studied. Here, we tested the ability of a well-known environmental neurotoxicant, methylmercury (MeHg), to induce hyperexcitability in medial prefrontal cortex (mPFC) excitatory pyramidal neurons, using whole cell patch-clamp recording. Acute MeHg exposure (20 µM) produced significant mPFC dysfunction, with a shift in the excitatory to inhibitory (E-I) balance toward increased excitability. Both excitatory postsynaptic current (EPSC) and inhibitory postsynaptic current (IPSC) charges were significantly increased after MeHg exposure. MeHg increased EPSC frequency, but there was no observable effect on IPSC frequency, EPSC amplitude or IPSC amplitude. Neither evoked AMPA receptor- nor NMDA receptor-mediated EPSC amplitudes were affected by MeHg. However, excitatory synapses experienced a significant reduction in paired-pulse depression and probability of release. In addition, MeHg induced temporal synchrony in spontaneous IPSCs, reflecting mPFC inhibitory network dysfunction. MeHg exposure also produced increased intrinsic excitability in mPFC neurons, with an increase in action potential firing rate. The observed effects of MeHg on mPFC reflect key potential mechanisms for neuropsychological symptoms from MeHg poisoning. Therefore, MeHg has a significant effect on mPFC circuits known to contribute to cognitive and emotional function and might contribute to etiology of neurodegenerative diseases, such as FTD.NEW & NOTEWORTHY Prefrontal cortical neurons are highly susceptible to glutamatergic excitotoxicity associated with neuronal degeneration in frontal dementia and to environmental toxicant exposure, one potential contributor to FTD. However, this has not been systematically studied. Our results demonstrate that methylmercury exposure leads to hyperexcitability of prefrontal cortical neurons by shifting excitatory to inhibitory (E-I) balance and raising sensitivity for spiking. Our results provide a mechanism by which environmental neurotoxicants may contribute to pathogenesis of diseases such as FTD.

A Novel Approach to Assessing the Joint Effects of Mercury and Fish Consumption on Neurodevelopment in the New Bedford Cohort.

Understanding health risks from methylmercury (MeHg) exposure is complicated by its link to fish consumption which may confound or modify toxicities. One solution is to include fish intake and a biomarker of MeHg exposure in the same model, but resulting estimates do not reflect the independent impact of accumulated MeHg or fish exposures. In fish-eating populations, this can be addressed by separating MeHg exposure into fish intake and average Hg content of the consumed fish. We assessed the joint association of prenatal MeHg exposure (maternal hair Hg) and fish intake (among fish-eating mothers) with neurodevelopment in 361 eight-year-olds from the New Bedford Cohort (born 1993-1998). Neurodevelopmental assessments used standardized tests of IQ, language, memory, and attention. Covariate-adjusted regression assessed the association of maternal fish consumption, stratified by tertiles of estimated average fish Hg, with neurodevelopment. Associations between maternal fish intake and child outcomes were generally beneficial for those in the lowest average fish Hg tertile, but detrimental in the highest average fish Hg tertile where, for example, each serving of fish was associated with 1.3 fewer correct responses (95% CI: -2.2, -0.4) on the Boston Naming test. Standard analyses showed no outcome associations with hair Hg or fish intake.

A Meta-Analysis of Mercury Biomagnification in Freshwater Predatory Invertebrates: Community Diversity and Dietary Exposure Drive Variability.

Accurate estimates of methylmercury (MeHg) exposure are valuable to actionably assess risk and protect wildlife and human health. MeHg trophic transfer is a critical driver of risk: MeHg is generally biomagnified by a factor of 8.3 ± 7.5 from one trophic level to the next, averaged across freshwater communities (mean ± standard deviation). This variability can produce disparate risks even where basal MeHg concentrations are similar. Taxonomy may be one driver of this variability: physiologically diverse groups, like vertebrates and invertebrates, may assimilate MeHg differently. To determine whether taxonomy affects trophic transfer efficiency, we conducted a meta-analysis characterizing predatory invertebrate MeHg biomagnification. Our analyses estimated that freshwater predatory invertebrates biomagnify MeHg by factors of 2.1 ± 0.2 to 4.3 ± 0.3, with a 98.9 ± 0.4% posterior probability that factors are below 5 (mean ± standard error). When vertebrates or primary producers were included, a site's trophic magnification factor was 18.6 ± 6.2 to 54.1 ± 7.7% higher than estimates for invertebrates alone. Biomagnification was inversely correlated to prey MeHg concentration and varied among systematic and functional groups. These data suggest that predatory invertebrates biomagnify MeHg less efficiently than vertebrates and that a community's diversity and structure determine its biomagnification efficiency. Incorporating organismal variation in trophic transfer estimates may improve the assessment, communication, and management of MeHg risk.

Microorganisms Involved in Methylmercury Demethylation and Mercury Reduction are Widely Distributed and Active in the Bathypelagic Deep Ocean Waters.

The ocean's mercury (Hg) content has tripled due to anthropogenic activities, and although the dark ocean (>200 m) has become an important Hg reservoir, concentrations of the toxic and bioaccumulative methylmercury (MeHg) are low and therefore very difficult to measure. As a consequence, the current understanding of the Hg cycle in the deep ocean is severely data-limited, and the factors controlling MeHg, as well as its transformation rates, remain largely unknown. By analyzing 52 globally distributed bathypelagic deep-ocean metagenomes and 26 new metatranscriptomes from the Malaspina Expedition, our study reveals the widespread distribution and expression of bacterial-coding genes merA and merB in the global bathypelagic ocean (∼4000 m depth). These genes, associated with HgII reduction and MeHg demethylation, respectively, are particularly prevalent within the particle-attached fraction. Moreover, our results indicate that water mass age and the organic matter composition shaped the structure of the communities harboring merA and merB genes living in different particle size fractions, their abundance, and their expression levels. Members of the orders Corynebacteriales, Rhodobacterales, Alteromonadales, Oceanospirillales, Moraxellales, and Flavobacteriales were the main taxonomic players containing merA and merB genes in the deep ocean. These findings, together with our previous results of pure culture isolates of the deep bathypelagic ocean possessing the metabolic capacity to degrade MeHg, indicated that both methylmercury demethylation and HgII reduction likely occur in the global dark ocean, the largest biome in the biosphere.

Competitive Binding Kinetics of Methylmercury-Cysteine with Dissolved Organic Matter: Critical Impacts of Thiols on Adsorption and Uptake of Methylmercury by Algae.

Complexes with low-molecular-weight thiols are crucial species of methylmercury (MeHg) excreted by anaerobic Hg-methylating microbes, notably, MeHg-cysteine (MeHg-Cys). As MeHg-Cys diffuses into surface water, it would undergo a ligand exchange process with dissolved organic matter (DOM) under nonsulfidic conditions, inevitably altering MeHg speciation and bioavailability to phytoplankton. In this study, we investigated the competitive binding kinetics between MeHg-Cys and Suwannee River natural organic matter, and their influence on the adsorption and uptake of MeHg by the cyanobacterium, Synechocystis sp. PCC6803. Liquid chromatography-inductively coupled plasma mass spectrometry was employed to monitor the kinetics processes involving competition of DOM with Cys for MeHg binding, which revealed that competitive binding kinetics were dictated by the abundance of thiol moieties in DOM. Thiol concentrations of 0.97 and 49.34 µmol of thiol (g C)-1 resulted in competitive binding rate constant (k values) of 0.30 and 3.47 h-1, respectively. Furthermore, the time-dependent competitive binding of DOM toward MeHg-Cys significantly inhibited MeHg adsorption and uptake by cyanobacteria, an effect that was amplified by an increased thiol abundance in DOM. These findings offer valuable insights into the kinetic characteristics of MeHg's fate and transport, as well as their impact on bioconcentration in aquatic organisms within natural aquatic ecosystems.

Single-cell ICP-MS for evaluating the Se-protective effect against MeHg+-induced neurotoxicity in human neuroblastoma cell line (SH-SY5Y).

The protective effect of selenium (Se) against Hg-induced neurotoxicity has been widely investigated; however, the mechanisms behind this interaction have not been fully elucidated yet. In the current work, the role of Se against MeHg+-induced cytotoxicity in the human neuroblastoma cell line (SH-SY5Y) is reported for the first time by tracking Hg uptake and accumulation at the single-cell level by inductively coupled plasma-mass spectrometry in single-cell mode (SC-ICP-MS). The influence of different Se species (SeMet, SeMeSeCys, citrate-SeNPs, and chitosan-SeNPs) on MeHg+ cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. SeMet and SeMeSeCys exhibited protective effects against MeHg+-induced cell death, particularly at high MeHg+ concentrations (LC50). In addition, chitosan-SeNPs showed greater protection compared to citrate-SeNPs when co-exposed with MeHg+. Interestingly, SC-ICP-MS unveiled the heterogeneous distribution of Hg uptake by SH-SY5Y cells. Co-exposure of SeMet and SeMeSeCys with MeHg+ led to a reduction of the amount of Hg accumulated per individual cell, which decreased the maximum level of Hg per cell by half (from 60 fg Hg cell-1 to 30 fg Hg cell-1) when SeMet was present, along with a decrease in the percentage of cells that accumulated the highest quantity of MeHg+. All these data corroborate the protective role of Se against Hg toxicity at the cellular level.

Fish intake and mercury exposure in young children.

Fish consumption is one of the main sources of mercury (Hg) exposure, but few studies have examined Hg exposure from fish consumption among children. This study aimed to assess the frequency of fish intake and associations with Hg and other element concentrations among 700 three-year-old children from the New Hampshire Birth Cohort Study. Usual fish intake was derived from a validated food frequency questionnaire (Block Questionnaire for ages 2-7) and toenail element concentrations were determined using ICP-MS. Multiple linear regression analysis was used to assess the association between fish intake and toenail element concentrations. A mixture analysis, using Weighted quantile sum (WQS) regression, was used to estimate the relative contribution of fish consumption to element exposures. Twenty-three percent of children were reported to consume at least one fish meal/week on average during the previous 6 months. In adjusted linear regression models, children with any type of fish consumption versus no consumption had 108% (95% confidence interval (CI: 68%, 153%)) higher toenail Hg concentrations. To a lesser extent, children consuming "other fish (not fried) including tuna" and "fried fish or fish sticks" had 120% (95% CI: 82%, 164%), and 23% (95% CI: 2%, 51%) higher toenail concentrations, respectively, than those consuming no fish. Using WQS regression, Hg was the element most strongly related to fish consumption. Fish intake among young children was related to Hg exposure even at low levels of consumption. Future studies will need to determine the health consequences of this exposure.

Methylmercury exposure and risk of wintering migratory birds in the Poyang Lake basin, China.

Mercury (Hg), especially methylmercury (MeHg), is a pervasive contaminant that poses significant risks to birds occupying high trophic levels. However, we have little knowledge about the mercury exposure and its risks for birds in Poyang Lake basin, China. Therefore, during 2020-2021, we investigated MeHg concentrations in breast feathers of wintering migratory birds (n = 430 from 43 species belonging to 9 orders) in Poyang Lake Nanji Wetland and Jiangxi Nanfengmian National Nature Reserve, China. MeHg concentrations in breast feathers varied greatly by species, foraging guilds and taxonomic orders, among which the highest concentration was detected in great egret (8849 ± 5975 ng g-1 dw). Comparing with studies worldwide, high MeHg concentrations in feathers of Ardeidae from Pelecaniformes were found in this area. Moreover, herons migrating between northern and southern China had lower MeHg concentration than residents in southern China related to habitat Hg. Considering the applicability and sensitivity of the equations for the transformation of MeHg concentrations in feathers to blood-equivalent total Hg (THg) values, method CJ that the equation based on songbirds was used for the transformation of the songbirds and the equation based on seabirds for the others performed better than other three for risk assessment of bird Hg in this study. 23.1% of birds from Poyang Lake were at risk of Hg exposure based on the method CJ. Carnivorous birds from Pelecaniformes had the highest risk levels, with 37.2% categorized as no risk (≤200 ng g-1 ww), 48.9% as low risk (200-1000 ng g-1 ww), 11.1% as moderate risk (1000-3000 ng g-1 ww), 1.1% as high risk (3000-4000 ng g-1 ww), and 1.7% as severe risk (>4000 ng g-1 ww). These risks suggest long-term monitoring and further advanced studies about freshwater waterbirds Hg exposure is necessary.

Temporal mercury dynamics throughout the rice cultivation season in the Ebro Delta (NE Spain): An integrative approach.

During the last few decades, inputs of mercury (Hg) to the environment from anthropogenic sources have increased. The Ebro Delta is an important area of rice production in the Iberian Peninsula. Given the industrial activity and its legacy pollution along the Ebro river, residues containing Hg have been transported throughout the Ebro Delta ecosystems. Rice paddies are regarded as propitious environments for Hg methylation and its subsequent incorporation to plants and rice paddies' food webs. We have analyzed how Hg dynamics change throughout the rice cultivation season in different compartments from the paddies' ecosystems: soil, water, rice plants and fauna. Furthermore, we assessed the effect of different agricultural practices (ecological vs. conventional) associated to various flooding patterns (wet vs. mild alternating wet and dry) to the Hg levels in rice fields. Finally, we have estimated the proportion of methylmercury (MeHg) to total mercury in a subset of samples, as MeHg is the most bioaccumulable toxic form for humans and wildlife. Overall, we observed varying degrees of mercury concentration over the rice cultivation season in the different compartments. We found that different agricultural practices and flooding patterns did not influence the THg levels observed in water, soil or plants. However, Hg concentrations in fauna samples seemed to be affected by hydroperiod and we also observed evidence of Hg biomagnification along the rice fields' aquatic food webs.

Multiple effects of carbon, sulfur and iron on microbial mercury methylation in black-odorous sediments.

Black-odorous sediments provide ideal conditions for microbial mercury methylation. However, the multiple effects of carbon, sulfur, and iron on the microbial methylmercury of mercury in black-odorous sediments remains unclear. In this study, we conducted mercury methylation experiments using sediments collected from organically contaminated water bodies, as well as black-odorous sediments simulated in the laboratory. The results showed that black-odorous sediments exhibit a high capacity for mercury methylation. By simulating the blackening and odorization process in sediments, it was confirmed that dissolved oxygen, organic matter and sulfide were the primary factors triggering the black-odorous phenomenon in sediments. Regarding the influence of key factors in sediments on methylmercury formation, the batch tests demonstrated that high concentrations of organics additions (above 200 mg/L) may reduce bacterial activity and weaken mercury methylation in sediments. Under five different iron-sulfur ratios, the concentrations of methylmercury in the black-odorous sediments showed an increasing trend, the ratio of 5.0 Fe/S exhibited the highest MeHg accumulation. The iron-sulfur ratio in the sediment had a significant effect on the mercury methylation process, which was mainly due to the competition between Fe2+ and Hg2+ for sulfide sites and the adsorption/coprecipitation of Hg2+ by FeS. These findings offer a potential avenue for further understanding and controlling mercury methylation, contributing to the mitigation of the potential threat of mercury pollution to the environment and human health.

Algal-derived dissolved organic matter accelerates mercury methylation under cyanobacterial blooms in the sediment of eutrophic lakes.

Mercury (Hg), especially in the form of methylmercury (MeHg), poses a significant threat to both organisms and the environment due to its extreme toxicity. While methylation process of Hg in sediments has been extensively studied, recognition of its associated risks and mechanisms during cyanobacterial blooms remains limited. This study investigated the distribution characteristics of Hg and MeHg in sediments of Taihu Lake, China. The concentration of Hg and MeHg varied within the range of 96.0-212.0 ng g-1 and 0.1-0.5 ng g-1, respectively. Higher ecological risks of Hg were found in algal-dominated regions compared to macrophyte areas. The significant correlations observed between Hg, MeHg, and algal-derived dissolved organic matter (ADOM) components C1 and C2 in algal-dominated regions indicate a close association between ADOM components and the Hg methylation process. These components are involved in the absorption or complexation of Hg, participate in redox reactions, and modulate microbial activity. The dsrB gene in sulfate-reducing bacteria (SRB) was found to accelerate the metabolic pathways of Hg methylation. These findings indicate that ADOM could enhance the methylation process of Hg during cyanobacterial blooms, which warrants attention.

Using live videography observation and Bayesian isotope mixing model to identify food composition and dietary contribution to inorganic mercury and methylmercury intake by songbird nestlings.

Mercury (Hg) exposure is increasing in terrestrial birds; however, studies on its sources are scarce. In the present study, we elucidated the food composition of green-backed tit nestlings from three urban forest parks (CPL, AHL, and LCG) using live videography observation (LVO). Furthermore, the daily dietary intakes of inorganic Hg (IHg) (MDIIHg) and methylmercury (MeHg) (MDIMeHg) were determined using the Bayesian isotope mixing model (BIMM) to uncover the nestlings' specific dietary Hg contribution. Both LVO and BIMM indicated that Lepidoptera (primarily caterpillar) constituted the primary food source for the nestlings in the three forests, accounting for approximately 60% of their diet in all three forest parks. The estimated MDI of Hg revealed that lepidopterans and spiders primarily contributed to IHg exposure, with a co-contribution ratio of 71.8%-97.7%. Unexpectedly, dietary MeHg was mostly derived from spiders; the highest contribution ratio of 93.6% was recorded at CPL, followed by another peak ratio of 92.9% at LCG. However, the dietary exposure was primarily IHg, accounting for 69.8% (AHL), 62.0% (LCG), and 61.3% (CPL) of the nestlings. Our study findings highlight the importance of dietary IHg transfer in evaluating the effects of Hg in nestlings. LVO, coupled with BIMM, is an effective tool for determining the food compositions of songbird nestlings and estimating the contribution of specific diets.

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.

Review: myogenic and muscle toxicity targets of environmental methylmercury exposure.

A number of environmental toxicants are noted for their activity that leads to declined motor function. However, the role of muscle as a proximal toxicity target organ for environmental agents has received considerably less attention than the toxicity targets in the nervous system. Nonetheless, the effects of conventional neurotoxicants on processes of myogenesis and muscle maintenance are beginning to resolve a concerted role of muscle as a susceptible toxicity target. A large body of evidence from epidemiological, animal, and in vitro studies has established that methylmercury (MeHg) is a potent developmental toxicant, with the nervous system being a preferred target. Despite its well-recognized status as a neurotoxicant, there is accumulating evidence that MeHg also targets muscle and neuromuscular development as well as contributes to the etiology of motor defects with prenatal MeHg exposure. Here, we summarize evidence for targets of MeHg in the morphogenesis and maintenance of skeletal muscle that reveal effects on MeHg distribution, myogenesis, myotube formation, myotendinous junction formation, neuromuscular junction formation, and satellite cell-mediated muscle repair. We briefly recapitulate the molecular and cellular mechanisms of skeletal muscle development and highlight the pragmatic role of alternative model organisms, Drosophila and zebrafish, in delineating the molecular underpinnings of muscle development and MeHg-mediated myotoxicity. Finally, we discuss how toxicity targets in muscle development may inform the developmental origins of health and disease theory to explain the etiology of environmentally induced adult motor deficits and accelerated decline in muscle fitness with aging.

Epigenetic alternations in the SYP and DLG4 genes due to low-level methylmercury exposure during neuronal differentiation in vitro.

Methylmercury (MeHg) is an environmental toxin known to damage the central nervous system. When pregnant women ingest seafood, which may contain accumulated MeHg, fetal development may be affected. The embryonic period, a time of major epigenetic change, is susceptible to epigenetic disruptions due to chemical exposure. Therefore, understanding the molecular mechanism underlying MeHg's effects on neuronal development requires consideration of epigenetic factors. In this study, we investigated epigenetic modifications in the synaptophysin (SYP) and discs large MAGUK scaffold protein 4 (DLG4) genes. LUHMES cells were exposed to 1 nM MeHg for 6 days during days 2-8 of neural differentiation. MeHg exposure significantly reduced the number of spikes observed on day 16 of differentiation. Both mRNA and protein expression levels of SYP and DLG4 were significantly decreased by MeHg exposure. Additionally, MeHg treatment reduced acetyl histone H3 levels associated with transcriptional activity in the SYP gene while increasing histone H3 lysine 27 tri-methylation (H3K27me3) levels related to transcriptional repression. Conversely, regarding the DLG4 gene, MeHg exposure increased H3K27me3 levels. Differential changes in DNA methylation (high and low methylation states) were observed in the SYP and DLG4 genes due to MeHg exposure depending on CpG site position. In conclusion, this study suggests that epigenetic changes, particularly histone modifications, contribute to decreased MeHg exposure-induced SYP and DLG4 expression during neuronal differentiation.

Molecular crosstalk and putative mechanisms underlying mitochondrial quality control: The hidden link with methylmercury-induced cognitive impairment.

Methylmercury (MeHg) is a neurotoxin associated with foetal neurodevelopmental and adult cognitive deficits. Neurons are highly dependent on the tricarboxylic acid cycle and oxidative phosphorylation to produce ATP and meet their high energy demands. Therefore, mitochondrial quality control (MQC) is critical for neuronal homeostasis. While existing studies have generated a wealth of data on the toxicity of MeHg, the complex cascades and molecular pathways governing the mitochondrial network remain to be elucidated. Here, 0.6, 1.2 and 2.4 mg/kg body weight of MeHg were administered intragastrically to pregnant Sprague Dawley rats to model maternal MeHg exposure. The results of the in vivo study revealed that MeHg-treated rats tended to perform more directionless repetitive strategies in the Morris Water Maze and fewer target-orientation strategies than control offspring. Moreover, pathological injury and synaptic toxicity were observed in the hippocampus. Transmission electron microscopy (TEM) demonstrated that the autophagosomes encapsulated damaged mitochondria, while showing a typical mitochondrial fission phenotype, which was supported by the activation of PINK1-dependent key regulators of mitophagy. Moreover, there was upregulation of DRP1 and FIS1. Additionally, MeHg compensation promoted mitochondrial biogenesis, as evidenced by the activation of the mitochondrial PGC1-α-NRF1-TFAM signalling pathway. Notably, SIRT3/AMPK was activated by MeHg, and the expression and activity of p-AMPK, p-LKB1 and SIRT3 were consistently coordinated. Collectively, these findings provide new insights into the potential molecular mechanisms regulating MeHg-induced cognitive deficits through SIRT3/AMPK MQC network coordination.

Algae decomposition released dissolved organic matter subfractions on dark abiotic mercury methylation.

To understand the mechanism of dark abiotic mercury (Hg) methylation by algae-derived dissolved organic matter (DOM) and effectively manage the environmental risks of mercury methylation in aquaculture areas, we investigated the influence of subfractions of DOM released from algae (Ulothrix sp.) decomposition on mercury methylation. The results showed that the hydrophobic basic component (HOB) in DOM exhibited the most substantial promotion effect on Hg methylation. The methylmercury (MeHg) production in the HOB treatment increased significantly, while the production rate of MeHg (%MeHg represented the concentration ratio of MeHg to THg) in the six subfractions treated solutions decreased significantly with the increase of Hg concentration. The change of the %MeHg was more evident at low Hg concentration, indicating the limited number of binding sites and methyl donors on DOM. As a consequence, Hg(Ⅱ) in the solution could not be converted into MeHg in equal proportion. Furthermore, the production of MeHg in solution was significantly reduced by the decomposed algae DOM, and its concentration was in the range of 0.017-0.085 ng·L-1 (significantly lower than undecomposed algal). The difference between the decomposed and the non-decomposed algae DOM reached a significant level (P < 0.05). When the DOM decayed for 20 and 30 days, the Hg methylation ability of DOM was weakened most obviously. During the decomposition process, considerable variations were observed among the subfractions, with HOB consistently playing a dominant role in Hg methylation. At the same time, the hydrophilic acid component exhibited a significant inhibitory effect on Hg methylation. Generally, the main components (e.g. HOB and HIA (hydrophilic acid component)) of DOM affecting mercury methylation were found in our study, which provided a better understanding of algae-derived DOM subfractions on the Hg methylation, in an attempt to prevent and control water pollution in aquaculture areas.