Scientists at the UNC School of Medicine have discovered that knocking out the gene NrCAM leads to an increase of dendritic spines on excitatory pyramidal cells in the brains of mammals. Other studies have confirmed that the overabundance of dendritic spines on this type of brain cell allows for too many synaptic connections to form between neurons – a phenomenon strongly linked to autism.The finding, published in The Journal of Neuroscience, adds evidence that NrCAM is a major player in neurological disorders. Previous UNC studies showed that knocking out the NrCAM gene caused mice to exhibit the same sorts of social behaviors associated with autism in humans.

“There are many genes involved in autism, but we’re now finding out exactly which ones and how they’re involved,” said Patricia Maness, PhD, professor of biochemistry and biophysics and senior author of the Journal of Neuroscience paper. “Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism but to see if we can improve dendritic spine abnormalities, which may underlie autism.

Maness’s finding comes on the heels of a report from Columbia University researchers who found an overabundance of the protein MTOR in mice bred to develop a rare form of autism. By using a drug to limit MTOR in mice, the Columbia researchers were able to decrease the number of dendritic spines and thus prune the overabundance of synaptic connections during adolescence. As a result, the social behaviors associated with autism were decreased. However, the drug used to limit MTOR can cause serious side effects, and it is located inside cells, making it a potentially difficult protein to target.

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