Outside of a few rare autism syndromes, autism appears to result from a complex and incompletely understood interplay of genes and experiences that alter early brain development. Researchers have used genetic engineering to introduce many autism-associated genes into mice and rats to see how they change behavior. Similarly, they’ve tested how a single stress, such as maternal infection during pregnancy, can produce autism-like behaviors in offspring.
At Neuroscience 2013, researchers from the University of Cincinnati and Cincinnati Children’s Hospital described how they created a more-complex animal model of autism.
Their ongoing study has involved more than 400 rats, which the researchers have exposed to various combinations of three experiences:
* To model psychological stress, some pregnant rats and their litters were housed in cages with a wire grid floor instead of standard bedding. (Previous animal studies have shown that maternal stress during early pregnancy predisposes offspring to autism.)
* To produce iron deficiency, some of the pups were fed diets with 90 percent less iron than is found in standard feed. (In the US, iron deficiency affects up to 15 percent of young children.)
* To model a toxic exposure, some of the pups were given water laced with manganese. (Manganese toxicity occurs in children from sources such as contaminated water and soy infant formula. Unlike adults, children’s digestive systems readily absorb this toxic metal.)
The researchers then assessed the offsprings’ behavior in terms of social interaction, hyperactivity, sensitivity to noises and problem-solving (mazes).
“We found that interactions of these three treatments produce effects not seen with a single treatment,” says lead researcher Robyn Amos-Kroohs. For instance, rats exposed to manganese and prenatal/early life stress tended to avoid social contact. Iron-deficient rats exposed to prenatal/early life stress were less able to navigated mazes. The researchers are still analyzing changes in other behaviors.
“It’s rare for studies to investigate behavioral consequences of more than one exposure at a time,” comments Alycia Halladay, Autism Speaks senior director for environmental and clinical sciences. “These findings will open up doors for researchers to better understand how multiple exposures – more like what people experience – affect a number of outcomes.”
“The creation of good animal models is critical to the long process of developing new medicines,” adds Dan Smith, Autism Speaks senior director for discovery neuroscience. “It’s what enables us to understand what happens between exposure to autism’s risk factors and the resulting behaviors, or symptoms.”