Epigenetic Interactions Between Flame Retardant Exposure and Autism Mutation
Robert F. Berman, Ph.D., Mari Golub, Ph.D., Isaac N. Pessah, Ph.D., Tram Anh Ta, Ph.D., Janine M. LaSalle, Ph.D.
University of California, Davis
NIEHS Grants R01ES015171, P01ES011269
NIEHS grantees studying the effects of flame retardant exposure on a mouse model of autism susceptibility found that the offspring of exposed mice had an increased risk for neurodevelopmental deficits associated with reduced sociability and learning. The work provides insight into the epigenetic interface of gene-environment interactions that are involved in the social and cognitive behaviors associated with neurodevelopmental disorders.
The researchers examined the effects of the flame retardant BDE-47 on the offspring of mice genetically modified to have a Mecp2 gene mutation (Mecp2(308)). Mutations in the epigenetic factor methyl-CpG binding protein 2 (MECP2), cause Rett syndrome, an X-linked autism spectrum disorder.
The study results showed gene-environment interactions occurred in the female, but not the male, offspring of the mice with the Mecp2 mutation. BDE-47 exposure had a negative impact on pup survival and learning in adult females. Female mice receiving perinatal exposure to the flame retardant had significantly lower DNA methylation levels in the adult brain, and these methylation levels correlated with decreased social behavior. However, the Mecp2 mutation reversed a social novelty-learning defect brought on by BDE-47 exposure, in a way that corresponded to increased levels of the methyltransferase Dnmt3a gene, which is required for learning and memory in the mouse brain.
Citation: Woods R, Vallero RO, Golub MS, Suarez JK, Ta TA, Yasui DH, Chi LH, Kostyniak PJ, Pessah IN, Berman RF, Lasalle JM. 2012. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2(308) mutation. Hum Mol Genet; doi:10.1093/hmg/dds046 [Online 15 February 2012].
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