Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an aluminum factory in China: A cross-sectional study

Shang, Nan; Zhang, Lan; Wang, Shuo; Huang, Tao; Wang, Yanhong; Gao, Xiaocheng; Xu, Shimeng; Zhang, Jingqi; Zhang, Ling; Niu, Qiao; Zhang, Qinli

doi:10.1016/j.ecoenv.2021.112110

Cited by 31 publications

(5 citation statements)

References 53 publications

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“…It has been documented that exposure to dangerous metals, including lead, cadmium, tungsten, and manganese, is related to lowered cognitive function [ 7 , 9 , 10 , 11 ]. However, it has also been discovered that some heavy metals, such as selenium and zinc, can benefit cognitive function [ 12 , 13 ]. Laboratory data suggest that there might be sex disparities regarding how heavy metals affect cognitive performance due to variations in hormone levels, body makeup, and brain architecture [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Sex Specificity in the Mixed Effects of Blood Heavy Metals and Cognitive Function on Elderly: Evidence from NHANES

et al. 2023

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The way that males and females react to environmental exposures and negative impacts on their neurological systems is often different. Although previous research has examined the cognitively impairing effects of solitary metal exposures, the relationship between metal mixtures and cognitive function, particularly when considering an individual’s sex, remains elusive. This study aimed to investigate the sex differences in the association between multiple metal combinations and cognitive function in older Americans. This research employed the 2011–2014 NHANES survey of elderly Americans. The association between five mixed metals and four cognitive tests (the animal fluency test (AFT), the digit symbol substitution test (DSST), the instant recall test (IRT), and the delayed recall test (DRT)) were investigated with generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression model (WQS), and quantile g-computation regression model (Qgcomp). A total of 1833 people, including 883 males and 950 females, enrolled in this cross-sectional study. We discovered that blood lead and blood cadmium were negatively associated with cognitive performance, while blood selenium demonstrated a positive association with cognitive function in older people. The negative relationship of heavy metal combinations on cognitive function might be somewhat reduced or even reversed via selenium. The IRT, AFT, and DSST are three of the four cognitive tests where men had more dramatic positive or negative results. There was a sex-specific connection between blood metal ratios and cognitive function among older Americans, as evidenced by the more significant relationship between mixed metals and cognitive performance in men (either positively or negatively). These results emphasize the impacts of ambient heavy metal exposure on cognitive function by employing sex-specific methods.

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Section: Introductionmentioning

confidence: 99%

Sex Specificity in the Mixed Effects of Blood Heavy Metals and Cognitive Function on Elderly: Evidence from NHANES

et al. 2023

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“…Our previous research results con rmed that Al-induced cognitive function impairment can cause changes in Al and Zn levels in the blood or brain in humans and rats, which preliminary explore the synergistic changes of Al and Zn in MCI (Shang et al, 2021;Shang et al, 2023). According to the literature, this synergistic effect was primarily caused by the competing absorption of different metals, the complex synthesis of different metals, and the effects of both on intracellular equilibrium (Mezzaroba et al, 2019).…”

Section: Introductionmentioning

confidence: 70%

“…This study was approved by the ethics and human subject committees of Shanxi Medical University and signed informed consent was also obtained from all the involved workers. The ICP-MS (inductively coupled plasma-mass-spectrometry) (NexION™300D, PerkinElmer Inc., USA) method was used to detect the concentrations of Al and Zn in serum due to its high sensitivity and accuracy (Shang et al, 2021). The sample pre-treatment steps include nitri cation at room temperature for 24 hours (the ratio of the sample and containing 0.1% Triton in 4% nitric acid is 0.4ml:1.6ml), centrifugation (13,600g for 15 min at 4 •C), lter the supernatant and ready for detection.…”

Section: Materials and Methods Of Investigation On Al-exposed Workersmentioning

confidence: 99%

Study on the mechanism of zinc finger proteins ROCK1 and DMD in zinc-mediated cognitive impairment caused by aluminum exposure

Shang,

Li,

Zhang

et al. 2024

Preprint

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Background: Aluminum (Al) exposure was implicated in neurodegenerative diseases and cognitive impairment, yet the involvement of zinc (Zn) and its mechanism in Al-induced mild cognitive impairment (MCI) remains poorly understood. Objective: Exploring the role of Zn in Al-induced cognitive impairment and its potential mechanisms. Methods: Montreal Cognitive Assessment (MoCA) test scores, and serum Al, Zn from Al industry workers were collected. A mediation analysis was performed to evaluate the role of serum Zn among serum Al and MoCA test scores. Subsequently, an Al-exposure study was conducted on a rat model categorized into control, low, medium, and high dose groups. After a Morris Water Maze test and detection of Al, Zn content in the hippocampus, integrated transcriptomic and proteomic analyses between the control group and the high-dose group were performed to identify the differentially expressed genes (DEPs), proteins (DEPs), and pathways. To corroborate these findings, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) were selected to identify the genes and proteins results. Results: Zn overall mediates the relationship between serum Al and cognitive function (mediation effect 17.82%, Effect value = -0.0351). In the Al-exposed rat model, 734 DEGs, 18 miRNAs, 35 lncRNAs, 64 circRNAs, and 113 DEPs were identified between the high-dose group and the control group. Among them, ROCK1, DMD, and other 4 DEPs were identified as related to Zinc finger proteins (ZNF). Co-enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) linked these changes to the RHOA/ROCK1 signaling axis. ZNF-related proteins Rock1, DMD, and DHX57 in the high-dose group were downregulated (p = 0.006, 0.003, 0.04), and the expression of Myl9, Rhoa, miR431, and miR182 was also downregulated (p = 0.003, 0.032, 0.032 and 0.046). These findings also show correlations between Al, Zn levels in the hippocampus, water maze performance and expressions of Myl9, Rhoa, miR431, miR182, DMD, ROCK1, and DHX57, with both negative and positive associations. Conclusion: Based on the results, we determined that Zn was involved in Al-induced MCI in Al workers and Al-exposed rat models. Al exposure and interaction with Zn could trigger the downregulation of ZNF of ROCK1, DMD, and DHX57. miR431, miR182 regulate RHOA/ROCK1 was one of the Zn-involved pathways in Al-induced cognitive impairment.

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“…A total of 400 µL of plasma and 4% 1.6 mL HNO 3 were mixed and digested at room temperature for 24 h, and the plasma aluminum concentration was detected by ICP-MS according to the methods described in previous publication (Shang et al 2021).…”

Section: Blood Aluminum Concentration Measurementmentioning

confidence: 99%

Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity

Song

Yuan

et al. 2023

Environ Sci Pollut Res

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Aluminum (Al) is a neurotoxic substance associated with cognitive dysfunction and neurodegenerative diseases, such as Alzheimer's disease, but the mechanisms for aluminum neurotoxicity remain to be identi ed. In this work, we try to investigate a novel potential biomarker of cognitive dysfunction following aluminum exposure and the mechanism involved. Recently, miR-134-3p was reported as a novel regulator of cognitive function. To address this, we investigate the expression level of miR-134-3p in plasma from 280 aluminum factory workers and analyzed the correlation between miRNA-134-3p, blood Al concentration, and Montreal Cognitive Assessment Scale (MoCA scale) score. The results implied that occupational aluminum exposure elevated miR-134-3p expression in the plasma of workers accompanied by cognitive impairment. Our experiment studies using both animal models and PC12 cells validated the up-regulation of miR-134-3p caused by aluminum. In addition, we identi ed that palmitoylation enzyme zDHHC3 was the target of miR-134-3p, and the decreasing AMPAR receptors (AMPARs) tra cking was related to the learning and memory impairment induced by aluminum. More importantly, using transfection and interference approaches in PC12 cells, inhibition of miR-134-3p resulted in a recovery of zDHHC3-AMPARs axis to a certain extent in response to aluminum. In summary, miR-134-3p was found to be involved in aluminum neurotoxicity by targeting zDHHC3-AMPARs axis and could serve as a potential biomarker or helpful target.

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Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an aluminum factory in China: A cross-sectional study

Cited by 31 publications

References 53 publications

Sex Specificity in the Mixed Effects of Blood Heavy Metals and Cognitive Function on Elderly: Evidence from NHANES

Sex Specificity in the Mixed Effects of Blood Heavy Metals and Cognitive Function on Elderly: Evidence from NHANES

Study on the mechanism of zinc finger proteins ROCK1 and DMD in zinc-mediated cognitive impairment caused by aluminum exposure

Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity

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