title: Bisphenol A induces oxidative stress and mitochondrial dysfunction in lymphoblasts from children with autism and unaffected siblings.
abstract: Autism is a behaviorally defined neurodevelopmental disorder. Although there is no single identifiable cause for autism, roles for genetic and environmental factors have been implicated in autism. Extensive evidence suggests increased oxidative stress and mitochondrial dysfunction in autism. In this study, we examined whether bisphenol A (BPA) is an environmental risk factor for autism by studying its effects on oxidative stress and mitochondrial function in the lymphoblasts. When lymphoblastoid cells from autistic subjects and age-matched unaffected sibling controls were exposed to BPA, there was an increase in the generation of reactive oxygen species (ROS) and a decrease in mitochondrial membrane potential in both groups. A further subdivision of the control group into two subgroups-unaffected nontwin siblings and twin siblings-showed significantly higher ROS levels without any exposure to BPA in the unaffected twin siblings compared to the unaffected nontwin siblings. ROS levels were also significantly higher in the autism vs the unaffected nontwin siblings group. The effect of BPA on three important mtDNA genes-NADH dehydrogenase 1, NADH dehydrogenase 4, and cytochrome b-was analyzed to observe any changes in the mitochondria after BPA exposure. BPA induced a significant increase in the mtDNA copy number in the lymphoblasts from the unaffected siblings group and in the unaffected twin siblings group vs the unaffected nontwin siblings. In all three genes, the mtDNA increase was seen in 70% of the subjects. These results suggest that BPA exposure results in increased oxidative stress and mitochondrial dysfunction in the autistic subjects as well as the age-matched sibling control subjects, particularly unaffected twin siblings. Therefore, BPA may act as an environmental risk factor for autism in genetically susceptible children by inducing oxidative stress and mitochondrial dysfunction.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA; Biology/Neuroscience Graduate Program, City University of New York Graduate Center, New York, NY 10016, USA; Center for Developmental Neuroscience and Developmental Disabilities, Staten Island, NY 10314, USA.
authors.forename: Kulbir
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
authors.forename: Ved
authors.initials: V
authors.lastname: Chauhan
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. Electronic address: abha.chauhan@opwdd.ny.gov.
authors.forename: Abha
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D001321:Autistic Disorder / Q000378:metabolism / Q000473:pathology*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D035781:Siblings; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004272:DNA, Mitochondrial; D016166:Free Radical Scavengers; D010636:Phenols; D017382:Reactive Oxygen Species; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Autism; Bisphenol A; Environment; Free radicals; Mitochondrial membrane potential; MtDNA copy number; Oxidative stress