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Monday, May 7, 2012

A Geneticist Explores a Pollutant's Effects

From www.AutismSpeaks.org Blog

Tuesday, April 24, 2012

Guest post by geneticist Janine LaSalle, Ph.D., of the University of California-Davis School of Medicine

I'm trained as a geneticist, but I suspect that genes are not the whole story when it comes to autism. More and more scientific evidence suggests that environmental influences are contributing to increasing rates of autism.

Many researchers tend to put genes and environment in separate boxes and study them separately. But others of us have come to realize that the genome does not exist in a lockbox away from environmental influences.

I have long been interested in how epigenetics help control brain development. Epigenetics is the study of influences on our DNA, other than gene mutations, that affect gene expression. Normal development and health depends, in part, on our cells having only the right genes turned on at the right level at a given time. [Editor’s note: Also see Alycia Halladay’s blog post on epigenetics and autism HERE.]

Recently we published the first study to look at how an environmental toxin affects epigenetics in a genetic mouse model of autism. This is important because epigenetic changes are potentially preventable and treatable. So understanding them better may lead to prevention and better treatments for autism spectrum disorder (ASD).

This study was designed by an interdisciplinary team of scientists at the University of California- Davis MIND Institute. Our goal was to look at a single gene implicated in autism and a single environmental exposure and study their interaction in mice. We focused on flame retardants called polybrominated diphenylethers, or PBDEs, which may impair the development of the nervous system. In recent years, levels of these chemicals have increased dramatically in our environment. Studies have also found rising levels of PBDEs in blood samples from children.

The gene we studied is called methyl CpG binding protein 2, or MECP2, for the protein it produces. This protein influences epigenetic activity important for normal brain development. Certain mutations to the gene are linked to Rett syndrome, an ASD.

Previously, an Autism Speaks grant allowed us to study the role of MECP2 in Rett Syndrome. In our new study, funded by the National Institute of Environmental Health Sciences, we used mice that were genetically engineered to have MECP2 mutations that predisposed them to autism-like behaviors. We then exposed the female mice to PBDE and studied the effects on the behavior of their pups. We also looked at epigenetic changes inside their brain cells. Specifically, we looked at DNA methylation, a chemical process that affects gene activity.

We found that offspring of the genetically altered mice exposed to flame retardants were smaller, less sociable and had learning and long-term memory problems – as compared with the pups of unexposed mice.

One surprising result was that decreased sociability and learning abilities showed up in exposed female pups, but not males. The females whose mothers were exposed to PBDE spent half as much time interacting with other mice than those whose mothers were not exposed. Importantly, these behavior problems corresponded to reduced DNA methylation in their brain cells.

While we should continue to question the need for flame retardant chemicals in our consumer products, the reality is that PBDEs are going to be in our environment for many years to come. Some research suggests that pregnant women may be able to reduce harmful effects of chemical exposures to their fetuses. For instance, a recent study looked at women taking prenatal vitamins in the months immediately before and after conception. This study did not look at exposure to PBDE or other environmental exposures. But it did suggest that prenatal vitamins may reduce the risk that a future child will develop autism. This may be because the folate in prenatal vitamins can help counter the effects of toxins on methylation.

Though these findings represent very early steps in the research progress, they have the potential to guide further research into the causes and prevention of autism. I’d like to thank the Autism Speaks community for making this research possible and for continuing to support the Children’s Center for Environmental Health at UC Davis.

Editor’s note: Thanks to the support of its families, donors and volunteers, Autism Speaks continued to fund a number of important studies on environmental risk factors for ASD. You can explore these and other Autism Speaks research using our Grant Search.

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