Interactions between cadmium, lead, mercury, and arsenic and depression: A molecular mechanism involved

• Published in: Journal of affective disorders Vol. 327; pp. 315 - 329
• Main Authors: Nguyen, Hai Duc, Kim, Min-Sun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 14.04.2023
• Subjects: Arsenic; Aryldialkylphosphatase; Cadmium; Depression; Humans; In silico; Mercury; MicroRNAs - genetics; Mixture of heavy metals; Molecular disease; Prospective Studies; Psychiatric/Mental Health; Selenium; Superoxide Dismutase-1; Transcription Factors; Depression; In silico; Mixture of heavy metals; Molecular disease
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2023.02.013

We aimed to assess the interactions between mixed heavy metals, genes, and miRNAs implicated in depression development and to design and create miRNA sponges. The key data-mining approaches in this study were the Comparative Toxicogenomics Database (CTD), MIENTURNET, GeneMania, Metascape, Webgestalt, miRNAsong, and Cytoscape software. A mixture of cadmium, lead, mercury, and arsenic was related to the development of depression. Even though the genes acquired from the heavy metals of depression studied were different, the “selenium micronutrient network”, “vitamin B12 and folate metabolism”, and “positive regulation of peptidyl-serine phosphorylation” pathways were highlighted. The heavy metal mixture altered the genes SOD1, IL6, PTGS2, PON1, BDNF, and ALB, highlighting the role of oxidative stress, pro-inflammatory cytokines, paraoxonase activity, neurotrophic factors, and antioxidants related to depression, as well as the possibility of targeting these genes in prospective depressive treatment. Chr1q31.1, five transcription factors (NR4A3, NR1H4, ATF3, CREB3L3, and NR1I3), the “endoplasmic reticulum lumen,” “blood microparticle,” and “myelin sheath”, were found to be important chromosomal locations, transcription factors, and cellular parts linked to depression and affected by mixed heavy metals. Furthermore, we developed a network-based approach to detect significant genes, miRNA, pathways, and illnesses related to depression development. We also observed eight important miRNAs related to depression induced by mixed heavy metals (hsa-miR-16-5p, hsa-miR-132-3p, hsa-miR-1-3p, hsa-miR-204-5p, hsa-miR-206, hsa-miR-124-3p, hsa-miR-146a-5p, and hsa-miR-26a-5p). In addition, we created and evaluated miRNA sponge sequences for these miRNAs in silico. A toxicogenomic design in silico was used. Our findings highlight the importance of oxidative stress, notably SOD1 and the selenium micronutrient network, in depression caused by heavy metal mixtures and provide additional insights into common molecular pathways implicated in depression pathogenesis. [Display omitted] •SOD1, IL6, PTGS2, PON1, BDNF, and ALB were related to mixed metals and depression.•Key pathways: selenium micronutrient network, B12, and folate metabolism•08 miRNAs induced by mixed heavy metals were implicated in depression development.•Eight miRNA sponge sequences for miRNAs were reported.