Mice with an extra copy of the autism-linked gene UBE3A develop abnormal social behaviors after experiencing recurrent seizures. The findings, presented Tuesday at the Autism Consortium Research Symposium in Boston, provide one possible explanation for why seizures and autism often go hand in hand.

They also suggest that seizures amplify the effects of autism risk genes. “It’s sort of a gene-environment interaction,” says lead investigator Matthew Anderson, associate professor of pathology at Beth Israel Deaconess Medical Center in Boston.

Roughly one in three people with autism also has epilepsy. These people tend to score lower on tests of social, motor and daily living skills than those who do not have epilepsy. But it’s unclear whether seizures lead to autism or whether the two simply share risk factors.

The researchers began probing the link between autism and epilepsy by injecting healthy mice with the seizure-inducing chemical pentylenetetrazole once daily for ten days. The animals experienced increasingly severe seizures over the course of the study. They also lost their innate preference to spend time with an unfamiliar mouse over an inanimate object — a social impairment revealed by the three-chamber social approach task.

Many mouse models of autism show the same social impairment, says Vaishnav Krishnan, a postdoctoral fellow in Anderson’s lab who presented the work. “We were able to show that seizures alone are able to cause the same thing, and these mice don’t have any genetic predisposition for autism,” Krishnan says.

Digging deeper:

The researchers cannot say for sure that the social impairments stem from seizures and not the drug itself. But Krishnan notes that other researchers have obtained similar results using different drugs that cause seizures. “We don’t think it’s purely a drug effect,” he says.

Following the seizures, the mice show dampened expression of PTEN, an autism-linked gene. This effect is seen mainly in the hippocampus, a brain region that is damaged in some people who have seizures.


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