期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 76, 期 -, 页码 25-33出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.07.030
关键词
Autism; Bisphenol A; Environment; Mitochondrial membrane potential; MtDNA copy number; Oxidative stress; Free radicals
资金
- NYS Institute for Basic Research in Developmental Disabilities
- Autism Research Institute, Autism Collaboration
- CUNY Graduate Center/CSI-CDNDD Program
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 SPA, 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. SPA 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 SPA 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. (C) 2014 Elsevier Inc. All rights reserved.
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