{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:58:36Z","timestamp":1791223116585,"version":"4.1.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>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\u2011receptor 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0359940","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:42:03Z","timestamp":1791222123000},"page":"e0359940","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network toxicology, molecular docking and molecular dynamics simulations for bisphenol A neurotoxicity in depression pathogenesis"],"prefix":"10.1371","volume":"21","author":[{"given":"Jinlian","family":"Zhang","sequence":"first","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhao","family":"Ma","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguo","family":"Lu","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmi","family":"Zhong","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xiong","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiliang","family":"Wu","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Chen","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4859-4343","authenticated-orcid":true,"given":"Ruikang","family":"Pang","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Nanning","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"1","key":"pone.0359940.ref001","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1186\/s12889-025-25561-4","article-title":"What do people need to know about endocrine disrupting chemicals and health? 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