Dose-dependent relationships between chronic arsenic exposure and cognitive impairment and serum brain-derived neurotrophic factor

Karim, Yeasir; Siddique, Abu Eabrahim; Hossen, Faruk; Rahman, Mizanur; Mondal, Victor; Banna, Hasan Ul; Hasibuzzaman, M.M.; Hosen, Zubaer; Islam, Md. Kamrul; Sarker, Md. Khalequzzaman; Nikkon, Farjana; Saud, Zahangir Alam; Lian, Xin; Himeno, Seiichiro; Hossain, Khaled

doi:10.1016/j.envint.2019.105029

Cited by 45 publications

(20 citation statements)

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“…Chronic exposure to levels of iAs above the World Health Organization (WHO) safety standard for drinking water (>10 lg=L) has been recognized to pose a significant risk of adverse outcomes across multiple organ systems (Mohammed Abdul et al 2015). Epidemiological studies in arsenic-affected areas of South America, Asia, and North America have demonstrated that chronic exposure to iAs is associated with adverse health effects, including increased risk for cardiovascular disease (Moon et al 2017), diabetes (Sung et al 2015), cognitive dysfunction (Karim et al 2019;Tyler and Allan 2014), adverse birth outcomes (Milton et al 2017), and overall mortality (Argos et al 2010). In addition, iAs exposure increases the risk for cancers of the skin (Karagas et al 2015), lung (Kuo et al 2017;Lamm et al 2015), bladder (Gamboa-Loira et al 2017;Kuo et al 2017), and kidney (Ferreccio et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Rare, Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study

Delgado

Chernoff

Huang

et al. 2021

Environ Health Perspect

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Background: Common genetic variation in the arsenic methyltransferase ( AS3MT ) gene region is known to be associated with arsenic metabolism efficiency (AME), measured as the percentage of dimethylarsinic acid (DMA%) in the urine. Rare, protein-altering variants in AS3MT could have even larger effects on AME, but their contribution to AME has not been investigated. Objectives: We estimated the impact of rare, protein-coding variation in AS3MT on AME using a multi-population approach to facilitate the discovery of population-specific and shared causal rare variants. Methods: We generated targeted DNA sequencing data for the coding regions of AS3MT for three arsenic-exposed cohorts with existing data on arsenic species measured in urine: Health Effects of Arsenic Longitudinal Study (HEALS, ), Strong Heart Study (SHS, ), and New Hampshire Skin Cancer Study (NHSCS, ). We assessed the collective effects of rare (allele frequency ), protein-altering AS3MT variants on DMA%, using multiple approaches, including a test of the association between rare allele carrier status (yes/no) and DMA% using linear regression (adjusted for common variants in 10q24.32 region, age, sex, and population structure). Results: We identified 23 carriers of rare-protein-altering AS3MT variant across all cohorts (13 in HEALS and 5 in both SHS and NHSCS), including 6 carriers of predicted loss-of-function variants. DMA% was 6–10% lower in carriers compared with noncarriers in HEALS [ (95% CI: , )], SHS [ (95% CI: , )], and NHSCS [ (95% CI: , )]. In meta-analyses across cohorts, DMA% was 8.7% lower in carriers [ (95% CI: , )]. Discussion: Rare, protein-altering variants in AS3MT were associated with lower mean DMA%, an indicator of reduced AME. Although a small percentage of the population (0.5–0.7%) carry these variants, they are associated with a 6–10% decrease in DMA% that is consistent across multiple ancestral and environmental backgrounds. https://doi.org/10.1289/EHP8152

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Section: Introductionmentioning

confidence: 99%

Rare, Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study

Delgado

Chernoff

Huang

et al. 2021

Environ Health Perspect

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“…Exposure to As may affect behavioral function through a direct action on the BDNF gene, given that As can alter DNA methylation patterns, possibly by interacting with transcription factor binding sites (TFBS) and inhibiting DNA repair mechanisms (Demanelis et al, 2019;Karim et al, 2019) (mechanisms of action shown in Fig. 3, numbers 1 and 2).…”

Section: Possible Effects Of As and CD On Neurobehavior Through Alteration Of Bdnf Expression Patternsmentioning

confidence: 99%

“…BDNF has been proposed as a biomarker of effect for brain functioning, allowing the exploration of potential causal pathways between exposure to particular endocrine disruptors (e.g., metals, bisphenol A, polycyclic aromatic hydrocarbons) and neurobehavioral outcomes in epidemiological studies (Kalia et al, 2017;Kundakovic et al, 2015;Mustieles et al, 2020;Perera et al, 2015;Tang et al, 2014). Exposure of humans to the neurotoxic environmental metals mercury (Hg) (particularly methyl-Hg), cadmium (Cd), lead (Pb), and arsenic (As) has been associated with disturbances in the pattern of BDNF synthesis, mainly detected as alterations in serum concentrations of total BDNF (Karim et al, 2019;Spulber et al, 2010;Y. Wang et al, 2016;Zhou et al, 2019;Zou et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Exploring the relationship between metal exposure, BDNF, and behavior in adolescent males

Rodríguez-Carrillo

Mustieles

D’Cruz

et al. 2022

International Journal of Hygiene and Environmental Health

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Background: Brain-derived neurotrophic factor (BDNF) plays an important role in brain development by regulating multiple pathways within the central nervous system. In the Human Biomonitoring for Europe Project (HBM4EU), this neurotrophin is being implemented as a novel effect biomarker to evaluate the potential threats of environmental chemicals on neurodevelopment. Objectives: To explore the relationships among exposure to environmental metals, BDNF biomarkers at two levels of biological complexity, and behavioral function in adolescent males. Methods: Data were gathered from 125 adolescents on: spot urine sample total concentrations of the neurotoxic metal(oid)s arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb); serum BDNF protein concentrations; and concurrent behavioral functioning according to the Child Behavior Check List (CBCL/6-18). In 113 of the participants, information was also collected on blood BDNF DNA methylation at six CpGs. Associations were evaluated by multivariate linear regression analysis adjusted for confounders. Results: As, Cd, Hg, and Pb were detected in 100%, 98.5%, 97.0%, and 89.5% of urine samples, respectively. Median serum BDNF concentration was 32.6 ng/mL, and total percentage of BDNF gene methylation was 3.8%. In the adjusted models, urinary As was non-linearly associated with more internalizing problems and Cd with more externalizing behaviors. The percentage BDNF DNA methylation at CPGs #5 and the mean percentage CpG methylation increased across As tertiles (p-trend = 0.04 and 0.03, respectively), while 2nd tertile and 3rd tertile of Cd concentrations were associated with lower serum BDNF and higher CpG3 methylation percentage. Additionally, when BDNF was categorized in tertiles, serum BDNF at the 3rd tertile was associated with fewer behavioral problems, particularly withdrawn (p-trend = 0.04), social problems (p-trend = 0.12), and thought problems (p-trend = 0.04). Conclusion: Exposure to As and Cd was associated with BDNF gene DNA methylation BDNF gene and serum BDNF, respectively. Associations with DNA methylation may be attributable to a higher variability over time in circulating BDNF concentrations than in the methylation status of this gene. Caution should be taken when interpreting the results relating postnatal Pb and Hg to behavioral functioning. Further studies are needed to verify these findings.

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“…Studies showed that prenatal exposure to a spectrum of polycyclic aromatic hydrocarbon (PAH)/aromatic pollutants may adversely affect early neurodevelopment, in part by reducing BDNF levels during the fetal period (26). A decreased BDNF level may be part of the biochemical basis of chronic arsenic exposure-related cognitive impairment (27). In addition, BDNF may also mediate the neurotoxic effects of polybrominated diphenyl ether congeners, dioxin, bisphenol A, nonylphenol, phthalate and particular matter exposure (28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Exposure to Perfluoroalkyl Substances During Pregnancy and Fetal BDNF Level: A Prospective Cohort Study

Luo

Nian

et al. 2021

Front. Endocrinol.

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BackgroundHumans are widely exposed to environmental perfluoroalkyl substances (PFAS), which may affect fetal neurodevelopment. Brain-derived neurotrophic factor (BDNF) is an important factor in neurodevelopment, but its role in PFAS-induced neurotoxicity is unclear. We investigated the association between prenatal PFAS exposure and fetal BDNF level in the umbilical cord blood in a large prospective cohort.MethodsA total of 725 pregnant women who participated in the Shanghai Birth Cohort were included. 10 PFAS were measured by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples of early pregnancy. The BDNF level was determined by ELISA. The concentration of total mercury (Hg) in the umbilical cord blood was tested by cold vapor atomic absorption spectrometry (AAS) and included as a main confounder, along with other covariates. Multiple linear regression was used to explore the associations between PFAS concentrations and BDNF level. Quantile-based g-computation was applied to explore the joint and independent effects of PFAS on BDNF level.ResultsThe mean BDNF level in the total population was 10797 (±4713) pg/ml. Male fetuses had a higher level than female fetuses (P<0.001). A significant positive association was observed between PFHxS and BDNF level after adjusting for potential confounders [β=1285 (95% CI: 453, 2118, P=0.003)]. No association was observed between other PFAS congeners and BDNF level. Results of the mixed exposure model showed that the joint effects of PFAS mixture were not associated with BDNF [β=447 (95% CI: -83, 978, P=0.10)], while the positive association with PFHxS exposure remained significant after controlling for other PFAS [β=592 (95% CI: 226, 958, P=0.002)]. The above associations were more prominent in male [β=773 (95% CI: 25, 1520, P= 0.04)] than female fetuses [β=105 (95% CI: -791, 1002, P= 0.82)] for the mixed effects.ConclusionsPrenatal exposure to PFHxS was associated with an increased BDNF level in the umbilical blood, especially in male fetuses.

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Dose-dependent relationships between chronic arsenic exposure and cognitive impairment and serum brain-derived neurotrophic factor

Cited by 45 publications

References 63 publications

Rare, Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study

Rare, Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study

Exploring the relationship between metal exposure, BDNF, and behavior in adolescent males

Exposure to Perfluoroalkyl Substances During Pregnancy and Fetal BDNF Level: A Prospective Cohort Study

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