INTERACTIONS OF PENTABROMODIPHENYL ETHERS WITH THYROID RECEPTOR IN INDIVIDUALS WITH AUTISTIC SPECTRUM DISORDER: an In Silico Evaluation

RIBEIRO R; ANDRADE BS; J CAPANI F; CALVALCANTE CVG; GIRALDEZ LD; MILAGRES MP; SANTOS G.

Congreso; Congreso de Psiquiatria Brasil; 2014

>Introduction: Persistent organic pollutants (POPs) are organic substances resistant to environmental process of degradation. Pentabromobiphenyl ethers (PBDS) belong to the group and may cause several impairments to human healthy. High levels of POPs, increase probabilities of children?s development of autism spectrum disorder (ASD).   Objectives: In silico evaluation of interactions of PBDEs with thyroid receptors in individuals with ASD. Methods: i) Gene Set Enrichment and Ontology of microarray of prefrontal cortex, hippocampal formation and cerebelar cortex of 6 subjects obtained from Alen Brain Atlas. ii) Co-expression network analysis (gene hub) of transcriptome profiles in hypothyroidism and epithelial permeability. iii) Molecular docking tests. Results: Centrality measures reveled two sub networks established by protein kinase (PRKC-alfa) and thyroid receptor gene (THRB) integrated by retinoic acid receptor (RARA). PKC-alfa is related to epithelial permeability (intestinal and blood brain barrier-BBB) and THRB regulate gene expression in complex with RARA. Molecular docking shows an incredible affinity (~ -6.4 Kcal/mol) between PBDEs (tetra, penta and hexabromobiphenyl ether) as a blocker of THRB. In summary it means a huge probability in development of thyroid dysfunction in new born as a result of POPs intoxication in domestic environment. High amount of PRKC lead to tight junction failure. This causes a leakiness of epithelial barrier in BBB and hence a traffic of molecules into the brain, a process that may play a central effect on ASD development. Conclusion: Our study suggests POPs (PBDEs) in domestic environment as a potential risk factor in development of hypothyroidism combined to epithelial permeability leakiness, tow remarkable co morbidity associate to ASD.