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BDNF as a potential mediator between childhood BPA exposure and behavioral function in adolescent boys from the INMA-Granada cohort

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  • معلومة اضافية
    • Contributors:
      Universidad de Granada = University of Granada (UGR); Institut de recherche en santé, environnement et travail (Irset); Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique EHESP (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ); École des Hautes Études en Santé Publique EHESP (EHESP); Département des sciences en santé environnementale (DEESSE); Departamento de Inteligencia Artificial UPM, Spain (DIA); Universidad Politécnica de Madrid (UPM); 733032; CD17/00212; PT17/0019; Ministerio de Educación, Cultura y Deporte, MECD: FPU 16/03011, FPU 17/01848, RYC-2016-20155; Instituto de Salud Carlos III, ISCIII: CP16/00085, FIS-PI17/01526; Universidad de Granada, UGR; European Regional Development Fund, ERDF: MS16/00085; Ministerio de Economía, Industria y Competitividad, Gobierno de España, MINECO
    • بيانات النشر:
      HAL CCSD
      Elsevier
    • الموضوع:
      2022
    • Collection:
      Université de Rennes 1: Publications scientifiques (HAL)
    • نبذة مختصرة :
      International audience ; Background: Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF). Objective: To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain). Methods: BPA concentrations were quantified by LC-MS/MS in spot urine samples from boys aged 9–11 years, normalized by creatinine and log-2 transformed. At adolescence (15–17 years), blood and urine specimens were collected, and serum and urinary BDNF protein levels were measured using immunoassays. DNA methylation levels at 6 CpGs in Exon IV of the BDNF gene were also assessed in peripheral blood using bisulfite-pyrosequencing. Adolescent's behavior was parent-rated using the Child Behavior Checklist (CBCL/6-18) in 148 boys. Adjusted linear regression and mediation models were fit. Results: Childhood urinary BPA concentrations were longitudinally and positively associated with thought problems (β = 0.76; 95% CI: 0.02, 1.49) and somatic complaints (β = 0.80; 95% CI: −0.16, 1.75) at adolescence. BPA concentrations were positively associated with BDNF DNA methylation at CpG6 (β = 0.21; 95% CI: 0.06, 0.36) and mean CpG methylation (β = 0.10; 95% CI: 0.01, 0.18), but not with total serum or urinary BDNF protein levels. When independent variables were categorized in tertiles, positive dose-response associations were observed between BPA-thought problems (p-trend = 0.08), BPA-CpG6 (p-trend ≤ 0.01), and CpG6-thought problems (p-trend ≤ 0.01). A significant mediated effect by CpG6 DNA methylation was observed (β = 0.23; 95% CI: 0.01, 0.57), accounting for up to 34% of the BPA-thought problems association. Conclusions: In line with toxicological studies, BPA exposure was longitudinally associated with increased BDNF DNA methylation, supporting the biological plausibility of BPA-behavior ...
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/34788942; hal-03368440; https://hal.science/hal-03368440; https://hal.science/hal-03368440/document; https://hal.science/hal-03368440/file/Mustieles-2022-BDNF%20as%20a%20potential%20mediator.pdf; PUBMED: 34788942
    • الرقم المعرف:
      10.1016/j.scitotenv.2021.150014
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.5CB0AF5