Autism in males linked to defect in brain immune function

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In a new study, researchers found that many cases of autism spectrum disorders (ASDs) may result from problems in immune cells that normally work to trim back unneeded brain connections in early life.

The research was led by scientists at Scripps Research.

ASDs are found in an estimated 2.4 percent of boys and 0.5 percent of girls.

They involve a variety of abnormalities including social skill deficits, repetitive behaviors, and hypersensitivities to sounds and light.

Research suggests that these disorders are largely genetic but can be caused by abnormalities in a variety of different genes acting alone or in combination.

To date, well over 100 gene mutations and variants have been linked to ASDs.

In the study, the team examined the effects of a set of gene mutations that account for a small percentage of autism disorders.

These mutations are known to cause a general overproduction of many proteins in brain cells, but how that overproduction leads to autism behaviors has been a mystery.

The scientists found evidence that the most relevant effect of this protein overproduction occurs in brain-based immune cells called microglial cells.

These cells normally prune unneeded brain connections, or synapses, as the brain develops in childhood.

Working in mice, the scientists determined that the protein overproduction impairs microglial cells in a way that hampers their synapse-pruning function, but only in males, leading to autism-like social behavior deficits.

The finding dovetails with the long-standing observation that autism disorders are four to five times more prevalent in males than females.

It is also consistent with recent evidence that in people with ASDs, the brain commonly has a higher number of synapses than normal.

The team says that impairments in microglia play a key role in the development of autism behaviors, at least in some cases, and may help explain the higher prevalence of autism disorders in males.

That, in turn, suggests that microglia might be a good target for future drugs that prevent or treat autism spectrum disorders.

The researchers now are following up with studies to discover precisely why protein increases affect microglia in males so much more than in females.

That discovery could prove to be an important piece of the puzzle of sex differences in autism—and could suggest new targets for autism treatments.

One author of the study is Baoji Xu, Ph.D., a professor in the Department of Neuroscience at Scripps Research.

The study is published in Nature Communications.

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