Contributors: Universidad de Granada = University of Granada (UGR); Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health (CIBERESP); 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); This research would not have been achieved without the selfless collaboration of the INMA-Granada adolescents and families who took part in the study. The authors also acknowledge the Human Genotyping Laboratory at the Spanish National Cancer Research Center, CeGen-PRB3, which is supported by grant no. PT17/0019, of the PE I+D+i 2013–2016, funded by the Instituto de Salud Carlos III (ISCIII) and ERDF. They thank the European Union's Horizon 2020 research and innovation program HBM4EU for financial support under Grant Agreement No. 733032. The study was also supported by the ISCIII with grant no. CP16/00085. The authors also acknowledge the funding received from the University of Granada for the open access publishing costs and the support of the Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), and the ISCIII (FIS 17/01526, FIS-PI16/01820 and FIS-PI16/01858). Vicente Mustieles and Shereen Cynthia D'Cruz were under contract with the HBM4EU project. A. Rodríguez-Carrillo received a predoctoral fellowship (FPU 16/03011) from the Spanish Ministry of Education and C. Freire (grant no. MS16/00085) received a grant under the Miguel Servet Type I program of the ISCIII ‘‘Fondo Europeo de Desarrollo Regional’’ (ISCIII/FEDER).; European Project: 733032,H2020,HBM4EU(2017)
نبذة مختصرة : International audience ; Background: Brain-derived neurotrophic factor (BDNF) plays an important role in brain development by regulating multiple pathways within the central nervous system. In the Human Biomonitoring for Europe Project (HBM4EU), this neurotrophin is being implemented as a novel effect biomarker to evaluate the potential threats of environmental chemicals on neurodevelopment. Objectives: To explore the relationships among exposure to environmental metals, BDNF biomarkers at two levels of biological complexity, and behavioral function in adolescent males. Methods: Data were gathered from 125 adolescents on: spot urine sample total concentrations of the neurotoxic metal(oid)s arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb); serum BDNF protein concentrations; and concurrent behavioral functioning according to the Child Behavior Check List (CBCL/6-18). In 113 of the participants, information was also collected on blood BDNF DNA methylation at six CpGs. Associations were evaluated by multivariate linear regression analysis adjusted for confounders. Results: As, Cd, Hg, and Pb were detected in 100%, 98.5%, 97.0%, and 89.5% of urine samples, respectively. Median serum BDNF concentration was 32.6 ng/mL, and total percentage of BDNF gene methylation was 3.8%. In the adjusted models, urinary As was non-linearly associated with more internalizing problems and Cd with more externalizing behaviors. The percentage BDNF DNA methylation at CPGs #5 and the mean percentage CpG methylation increased across As tertiles (p-trend = 0.04 and 0.03, respectively), while 2nd tertile and 3rd tertile of Cd concentrations were associated with lower serum BDNF and higher CpG3 methylation percentage. Additionally, when BDNF was categorized in tertiles, serum BDNF at the 3rd tertile was associated with fewer behavioral problems, particularly withdrawn (p-trend = 0.04), social problems (p-trend = 0.12), and thought problems (p-trend = 0.04). Conclusion: Exposure to As and Cd was associated with BDNF gene DNA methylation ...
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