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Mice With Autism Has Striking Similarities to Humans With Autism Spectrum Disorders

by Savitha C Muppala on  October 3, 2011 at 3:09 PM Mental Health News   - G J E 4
The behaviour and symptoms of mice with autism closely resembles humans suffering autism spectrum disorders.
 Mice With Autism Has Striking Similarities to Humans With Autism Spectrum Disorders
Mice With Autism Has Striking Similarities to Humans With Autism Spectrum Disorders
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According to researchers who report their findings in the September 30th issue of Cell, a Cell Press publication, the mouse model offers a window into the biological mechanisms that underlie the disease and its symptoms, and it provides a promising new way to test novel therapeutic strategies.

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"There were multiple lines of evidence highlighting this gene," said Daniel Geschwind of the University of California, Los Angeles.

In some cases, rare variants of the gene in question, known as CNTNAP2 (contactin associated protein-like 2), have been shown to cause an inherited form of autism syndrome known as cortical dysplasia-focal epilepsy syndrome (CDFE). More common variants in this gene have also been linked to autism risk in the general population, and CNTNAP2 appears to play an important role in brain circuits responsible for human language.

In the new study, the researchers developed mice lacking CNTNAP2 and find that the animals display many features of human autism. While the mice have normal visual and spatial memory, sensorimotor integration, and anxiety responses, they exhibit abnormal vocal communication and subnormal social interaction and repetitive behaviors. The mice are also hyperactive and suffered epileptic seizures, as do patients with CDFE.

A closer look at the animals' brains revealed problems in development of the neural circuitry. These problems include abnormal migration of neurons, fewer interneurons, and abnormal activity of the neuronal network. Interneurons connect neurons that carry impulses to the central nervous system to those that send impulses back out to the rest of the body.

Geschwind said their observations are consistent with emerging theories suggesting that autism is characterized in the brain with "long-range disconnectivity and short-range increases in connectivity."

It is not yet known whether people with CDFE have the interneuron deficiency seen in the mice, but the overall parallels are striking.

"I did not have high expectations necessarily," Geschwind said. "I did not necessarily expect to see the same behaviors in mice as in humans because we don't know how conserved the pathways are. This suggests they are very conserved � surprisingly so."

The mutant animals respond well to treatment with risperidone, an antipsychotic drug that was the first to win FDA approval for treating symptoms of autism spectrum disorder. Animals given the drug were less hyperactive, showed less repetitive grooming behavior and were better at building nests. Consistent with what had been seen previously in human patients, the mice did not show improvement in social interactions.

"It suggests at least the repetitive behaviors are conserved," Geschwind said. "We can hope that the social behaviors might also be."



Source: Eurekalert
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