Researchers aiming to understand why autism spectrum disorders (ASD) are more common in boys have discovered differences in a brain signalling pathway involved in reward learning and motivation that make male mice more vulnerable to an autism-causing genetic glitch.
“We don’t understand what it is about this disorder that predisposes boys as compared to girls to develop autism. One intriguing aspect of autism is that it predominantly affects males; four boys are affected for every one girl,” says senior study author Ted Abel, PhD, director of the Iowa Neuroscience Institute at the University of Iowa Carver College of Medicine.
“This is some of the first evidence in a mouse model of autism of a ‘female protective effect,’ from the behavioural to the molecular level,” says Nicola Grissom, first author of the study who is now an assistant professor of psychology at the University of Minnesota.
She added, “These findings shed valuable new light on the science of neurodevelopmental disorders, many of which are more common in boys. However, they also address the broader question of how sex and gender influence the neurobiology of how we learn and behave, which may be involved in the different levels of risk between women and men for developing many other neuropsychiatric conditions, as well.”
The level of D2 expression did not increase in the female autism mice. Abel notes that risperidone, one of very few drugs that is approved by the Food and Drug Administration to treat ASD symptoms, targets D2 dopamine receptors.
“We think we are on the right track,” Abel says. “We have begun to identify what may be an underlying reason why neurodevelopmental disorders predominantly affect boys, and that involves the function of the striatum and reward learning. This has implications for how we think about the underlying behavioural differences in autism and implications for how we develop both behavioural or pharmacological therapies to improve the lives of those with autism.”
The new findings are part of a bigger study where Abel and his colleagues are investigating many different mouse models of autism, in which different autism-linked genes have been disrupted. The researchers are seeking commonalities among the different models. One emerging theme, supported by the new study, is that a deficit in reward learning may be a common feature of ASD, and males are specifically deficient in this type of behaviour.
Abel notes that funding from the Simons Foundation was critical to the success of the project.
Source: News Medical Net