{
  "abstract": "Bisphenol A (BPA), a widespread environmental endocrine disruptor, can cross the blood-brain barrier and exert neurotoxic effects closely associated with depression pathogenesis. However, the precise molecular targets and signaling pathways mediating BPA-induced depression remain poorly understood. This study integrated network toxicology, molecular docking, molecular dynamics simulation, GEO transcriptomic dataset analysis, and in vivo experimental validation in mice to systematically investigate the potential toxicological targets and underlying mechanisms of BPA in depression. BPA-related targets were predicted from ChEMBL, STITCH, and SwissTargetPrediction, and depression-associated targets were retrieved from GeneCards, OMIM, and TTD databases. Overlapping targets were subjected to PPI network construction, as well as GO and KEGG enrichment analyses. Molecular docking and 100 ns molecular dynamics simulations were performed to verify the binding affinity and structural stability between BPA and hub targets. A total of 29 overlapping targets were screened, which were significantly enriched in neural synaptic function, neurotransmitter binding, and the neuroactive ligand‑receptor interaction pathway. Five core hub genes including INS, ESR1, SLC6A4, GRIA1, and NTRK2 were identified, all of which exhibited stable specific binding to BPA with favorable binding free energies. Further validation based on multiple GEO datasets confirmed that these five core genes were markedly downregulated in MDD patients, accompanied by significant suppression of neurotrophic and insulin-related pathways. In vivo animal experiments further demonstrated that BPA exposure aggravated depressive-like behaviors in mice and significantly downregulated both mRNA and protein expression of the five core molecules in brain tissues. Collectively, this study identifies key neurotoxicity-related targets and molecular pathways underlying BPA-induced depression, providing a theoretical foundation for future mechanistic investigation and clinical intervention strategies.",
  "abstract_shown": true,
  "affiliations": [
    "The Eighth People’s Hospital of Nanning, Nanning, Guangxi, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jinlian Zhang"
    },
    {
      "name": "Yuanhao Ma"
    },
    {
      "name": "Miguo Lu"
    },
    {
      "name": "Xiaohuan Jiang"
    },
    {
      "name": "Qingmi Zhong"
    },
    {
      "name": "Yan Zhang"
    },
    {
      "name": "Yan Xiong"
    },
    {
      "name": "Qiliang Wu"
    },
    {
      "name": "Lina Chen"
    },
    {
      "name": "Ruikang Pang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cv0799k62fp2p.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359940",
  "fulltext_url": null,
  "id": "cv0799k62fp2p",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0359940",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2307|Effects and risks of endocrine disrupting chemicals"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Biochemical simulations"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Hormones/Estrogens"
    ],
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      "plos",
      "/Biology and life sciences/Computational biology/Biochemical simulations"
    ],
    [
      "plos",
      "/Biology and life sciences/Toxicology/Predictive toxicology"
    ],
    [
      "plos",
      "/Biology and life sciences/Toxicology/Toxicity"
    ],
    [
      "plos",
      "/Ecology and environmental sciences/Environmental chemistry/Pollutants"
    ],
    [
      "plos",
      "/Medicine and health sciences/Mental health and psychiatry/Mood disorders/Depression"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Predictive toxicology"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Toxicity"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular docking"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular dynamics"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Environmental chemistry/Pollutants"
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  "openalex": "W7220445036",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0359940&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/cv0799k62fp2p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pone.0359940",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0359940"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "plos:environmental chemistry",
      "subfield": "environmental"
    },
    {
      "field": "chemistry",
      "origin": "plos:computational chemistry",
      "subfield": "theoretical"
    },
    {
      "field": "medicine",
      "origin": "plos:toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Network toxicology, molecular docking and molecular dynamics simulations for bisphenol A neurotoxicity in depression pathogenesis",
  "title_text": "Network toxicology, molecular docking and molecular dynamics simulations for bisphenol A neurotoxicity in depression pathogenesis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/cv0799k62fp2p",
  "venue": "PLOS One",
  "versions": []
}