RT Journal Article
T1 Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach.
A1 Rodriguez-Carrillo, Andrea
A1 D'Cruz, Shereen C
A1 Mustieles, Vicente
A1 Suarez, Beatriz
A1 Smagulova, Fatima
A1 David, Arthur
A1 Peinado, Francisco
A1 Artacho-Cordon, Francisco
A1 Lopez, Luis C
A1 Arrebola, Juan P
A1 Olea, Nicolas
A1 Fernandez, Mariana F
A1 Freire, Carmen
K1 Adolescents
K1 BDNF
K1 Behavior
K1 Effect biomarkers
K1 HBM4EU
K1 Non-persistent pesticides
AB Numerous contemporary non-persistent pesticides may elicit neurodevelopmental impairments. Brain-derived neurotrophic factor (BDNF) has been proposed as a novel effect biomarker of neurological function that could help to understand the biological responses of some environmental exposures. To investigate the relationship between exposure to various non-persistent pesticides, BDNF, and behavioral functioning among adolescents. The concentrations of organophosphate (OP) insecticide metabolites 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), malathion diacid (MDA), and diethyl thiophosphate (DETP); metabolites of pyrethroids 3-phenoxybenzoic acid (3-PBA) and dimethylcyclopropane carboxylic acid (DCCA), the metabolite of insecticide carbaryl 1-naphthol (1-N), and the metabolite of ethylene-bis-dithiocarbamate fungicides ethylene thiourea (ETU) were measured in spot urine samples, as well as serum BDNF protein levels and blood DNA methylation of Exon IV of BDNF gene in 15-17-year-old boys from the INMA-Granada cohort in Spain. Adolescents' behavior was reported by parents using the Child Behavior Check List (CBCL/6-18). This study included 140 adolescents of whom 118 had data on BDNF gene DNA methylation. Multivariable linear regression, weighted quantile sum (WQS) for mixture effects, and mediation models were fit. IMPy, MDA, DCCA, and ETU were detected in more than 70% of urine samples, DETP in 53%, and TCPy, 3-PBA, and 1-N in less than 50% of samples. Higher levels of IMPy, TCPy, and ETU were significantly associated with more behavioral problems as social, thought problems, and rule-breaking symptoms. IMPy, MDA, DETP, and 1-N were significantly associated with decreased serum BDNF levels, while MDA, 3-PBA, and ETU were associated with higher DNA methylation percentages at several CpGs. WQS models suggest a mixture effect on more behavioral problems and BDNF DNA methylation at several CpGs. A mediated effect of serum BDNF within IMPy-thought and IMPy-rule breaking associations was suggested. BDNF biomarkers measured at different levels of biological complexity provided novel information regarding the potential disruption of behavioral function due to contemporary pesticides, highlighting exposure to diazinon (IMPy) and the combined effect of IMPy, MDA, DCCA, and ETU. However, further research is warranted.
PB Academic Press
YR 2022
FD 2022-03-10
LK http://hdl.handle.net/10668/22209
UL http://hdl.handle.net/10668/22209
LA en
NO Rodríguez-Carrillo A, D'Cruz SC, Mustieles V, Suárez B, Smagulova F, David A, et al. Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach. Environ Res. 2022 Aug;211:113115.
NO 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 acknowledge the European Union's Horizon 2020 research and innovation program HBM4EUfor the financial support under Grant Agreement #733032. The study was also supported by the ISCIII with grants no. CP16/00085 and FIS 17/01526, and the Human Genotyping Laboratory at the Spanish National Cancer Research Center (CeGen-PRB3). The authors also thank the support of the Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), and the University of Granada (Grant “UNETE,” UCE-PP2017-06). A. Rodríguez-Carrillo received a predoctoral fellowship (FPU 16/03011) from the Spanish Ministry of Education, Spain, and Vicente Mustieles and Shereen Cynthia D'Cruz were under contract with the HBM4EUproject. C. Freire received a grant under the Miguel Servet Type I program of the ISCIII ‘‘Fondo Europeo de Desarrollo Regional’’ (MS16/00085; ISCIII/FEDER). This article forms part of the doctoral thesis developed by Andrea Rodríguez-Carrillo in the context of the “Clinical Medicine and Public Health Program” of the University of Granada (Spain).
DS RISalud
RD Apr 7, 2025