IMFAR 2013 – BPA Exposure – North Carolina State University

Environmental Impacts On the Brain and Behavior

https://imfar.confex.com/imfar/2013/webprogram/Paper12629.html

H. Patisaul, North Carolina State University, Raleigh, NC

Background:

Although it has long been suspected that environmental factors such as chemical contaminants, dietary components, infection or even maternal stress might contribute to autism, there is a paucity of data demonstrating a clear link.

However, a wide range of animal studies, across a diverse array of species, have found that exposure to endocrine disruptors during critical periods of development can induce behavioral changes such as increased anxiety, hyperactivity, and altered social behavior. 

This talk will summarize data from our lab and others demonstrating that exposure to chemicals during critical periods of developmental can induce behavioral changes consistent with components of autism spectrum disorders (ASDs).  Associated neural changes which may help identify the underlying mechanisms for these behavioral changes will also be highlighted.

Objectives:

The goal of our ongoing studies is to explore the behavioral and neural impacts of developmental exposure to endocrine disrupting compounds and identify potential modifying or mitigating factors such as diet.

Methods:

Using a wide variety of behavioral testing paradigms (elevated plus maze and similar) and rodent species, we are assessing how early life exposure to endocrine disruptors, specifically, the plastics component Bisphenol A (BPA), soy phytoestrogens, and a newly discovered fire retardant, Firemaster 550 (FM 550), alter social and affective behaviors across the lifespan.  To understand the mechanisms by which these behavioral effects are conferred, we use a variety of techniques including immunohistochemistry and RT-PCR arrays to identify associated changes in the brain.  Our primary focus is on limbic structures important for modulating social and affective behaviors, such as the amygdala and paraventricular nucleus (PVN).

Results:

Rats of both sexes, perinatally exposed to a human-relevant dose of BPA were more anxious in adolescence and adulthood but these effects were mitigated by a soy-rich diet, suggesting that dietary factors may be protective.

In the amygdala, expression levels of the beta form of the estrogen receptor (ESR2; p < 0.002) and a melanocortin receptor (MC4R; p < 0.01) were downregulated by BPA exposure.  These genes are required for oxytocin, release suggesting that the oxytocin/vasopressin system, which is well recognized to be important for social behavior and bonding, may be vulnerable to chemical insult. 

In the monogamous prairie vole, BPA exposed females were hyperactive, an effect consistent with what has been reported in young girls.  Emerging data from our lab also reveals that FM 550 alters anxiety levels in rats of both sexes.

Conclusions:

Collectively, these data support the hypothesis that environmental exposures during critical windows of development may contribute to behavioral characteristics contained within the autism spectrum.  The consistency and reproducibility of behavioral effects across species is particularly strong supporting evidence for the idea that chemical exposures may contribute to autism risk. Strategies for utilizing this data to better understand how endocrine disruptors and other environmental contaminants may be contributing to autism and related disorders will also be discussed.

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This entry was posted in Autism, co-morbid, Environment, Epigenetics, Genetics, Neurology, Treatment. Bookmark the permalink.

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