New evidence for flame retardant’s role in autism

A new study has for the first time, reported that the environment and genetics can work together to create autism-like symptoms in mice exposed in the womb to a flame retardant. The female mice — born to mothers that are genetically more susceptible to develop autistic behaviours — were less social and had impaired memories and learning skills after their mothers were exposed to a brominated compound known as a PBDE. A mother’s exposure to a flame retardant before, during and after pregnancy interacted with a known genetic mutation to impair learning and memory and decrease social behaviours in her offspring, a study with mice has found. Female mice were more sensitive to the exposure, which altered the on/off switches in the epigenetic code. This is the first study to link genetic, epigenetic and behavioural changes to a flame retardant chemical in females with a high genetic risk for autism spectrum disorders. The study is important because it focused on a specific gene mutation linked to Rett’s syndrome – a condition on the autism spectrum that primarily affects females. The results suggest that genetic risk for social deficits can interact with an environmental chemical to tip the balance toward exacerbated autistic behaviours. An individual with genetic risks for other health-related problems or diseases may also be more sensitive to these environmental chemicals than the overall general population. During the past 25 years, brominated flame retardants – including polybrominated diphenyl ethers (PBDEs) – have been used in home furnishings and electronics to slow their burning during a fire. PBDEs are routinely detected in household dust, food and air. PBDEs have a similar chemical structure to thyroid hormone and can mimic thyroid actions, which can lead to changes in brain development. Previous rodent studies have demonstrated that early life PBDE exposure increases activity, impairs learning and alters motor development. Some of the cell populations in the brain affected in autism are also sensitive to thyroid hormone regulation, and thus may be affected by PBDEs. Thyroid hormone acts on most cells in the body and plays a wide-ranging role in metabolism, growth and development. Hallmarks of autism spectrum disorder (ASD) include deficiencies in social behaviours, cognition and communication, often with repetitive behaviours. Recent evidence in the United States places ASD at as high as 1 in 88 children. It is known that environmental exposures and genetic susceptibility work in concert to increase the risk of developing disorders along the autism spectrum. PBDEs have been accumulating in the environment at the same time as the accelerating rise in ASDs. Because changes in the brain and other symptoms are similar in PBDE exposures and autism, the authors suggest that the two may be related. During the new study, the researchers investigated the interactions between genetics and environment. Adult female mice with a known genetic mutation were exposed orally every day for 10 weeks to one type of PBDE before, during and after pregnancy. The mother mice were genetically engineered with a truncated Mecp2 gene that makes the animals display fewer social behaviours, and learning and memory deficiencies. This mouse type is frequently used to model Rett’s syndrome because patients with Rett’s have similar Mecp2 deficiencies. Rett’s syndrome is a progressive disorder that lies within the autism spectrum. It is characterised by significant deficits in social behaviours and communication. Mecp2-truncated females were exposed daily from before conception to after weaning to 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), the most prevalent PBDE found in human blood. Doses were similar to those found within people. Offspring were measured throughout development for epigenetic and behavioural changes. Epigenetics describes modifications on the structure of the DNA and mediates some of the environmental influences on gene regulation. Mecp2 binds to methylated DNA, one type of epigenetic modification. PBDE levels within the brains of mice exposed to BDE-47 were similar to human post-mortem brain samples, showing that the doses used in this study were highly relevant to human exposure. PBDE exposure reduced social behaviour in both the mice with the truncated gene and normal mice used as controls in the study. Similar to Rett’s patients, the effects were even stronger in female mice with the genetic mutation. For instance, in Mecp2 truncated female mice, PBDE exposure reduced vocalisations in the young and decreased learning and long-term memory in adults. As adults, learning, memory and social interactions were impaired. Female mice with the mutation were also less fertile and offspring were smaller in body weight. The DNA methylation levels decreased in females exposed to PBDEs and this corresponded to reduced social behaviour. Males did not show any of these changes. Importantly, this study shows that in a genetically susceptible population, PBDE exposure can have strong effects and can tip the balance toward an autistic pattern of behaviours. The researchers examined the role of a single environmental chemical in autistic behaviours but did not design their experiments to prove cause and effect with flame retardants. This study is an important step in showing that low dose chemical exposures can be important risk factors in sensitive populations for social and neurological diseases.

Environmental Health News, 10 July 2012 ; ;