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Study May Shed Light on Autism and Brain Inflammation

Researchers working with mice see early evidence that it might be possible to treat some types of autism by “rebalancing” immune system
November 16, 2014

Researchers at Neuroscience 2014 are reporting new insights into the role that one class of immune cells may play in the brain inflammation seen in some children and adults with autism. Though preliminary, their findings suggest the possibility of someday treating certain forms of autism by “rebalancing” the immune system.

“We’re starting to understand how the peripheral immune system can affect brain function and behavior,” says neuroscientist Anthony Filiano, who is leading the study at the University of Virginia, Charlottesville. “This is exciting because we can target the immune system in ways we can’t target the brain.” Dr. Filiano works in the neuroscience laboratory of Jonathan Kipnis, at the university’s Center for Brain Immunology and Glia (BIG).

Dr. Filiano designed a study that built on earlier research in both mice and people. Previous mouse studies have shown that maternal inflammation during pregnancy can result in offspring with brain inflammation and autism-like behaviors. Along these lines, several studies looking at medical records have shown that mothers who have infections and/or signs of inflammation during pregnancy are more likely to have children who develop autism spectrum disorder (ASD). In addition, studies have found signs of inflammation in the brains of those affected by ASD.

Inflammation is the body’s normal infection-fighting response. However, problems can arise when inflammation becomes chronic, or fails to shut off after a threat has passed.

Working with T-cell deficient mice
In his new study, Dr. Filiano explored the idea that chronic brain inflammation and autism may result from a lack of T cells in the tissues that surround the brain.

T cells belong to the peripheral immune system, which guards against infection outside the brain. Such cells can’t enter the brain. Instead, the brain is patrolled by specialized immune cells called microglia. However, T cells appear to produce chemicals that can cross into the brain and direct microglia to support the healthy development of brain cells. Among the tasks that microglia perform is the pruning away of excess connections between neurons (brain nerve cells) during brain development.

In his new study, Dr. Filiano is using a line of mice genetically engineered to lack T cells. His team has noted three important abnormalities in these mice:

*The T-cell deficient mice spent less time socializing with other mice.

*Their microglia (brain immune cells) were in an “activated,” or inflammatory, state.

* Brain regions associated with social behavior in the mice showed signs of abnormal hyperconnectivity. Indirectly, this suggests that the microglia failed to perform their task of pruning excess connections between brain cells.

Restoring normal behavior
Working with the T-cell deficient mice, the researchers next showed that they could restore normal social behavior with a transplant of T cells from ordinary mice.

These early findings suggest that T cells and microglia work together to support healthy brain development, Dr. Filiano says. “We think the T cells are doing this by producing signaling molecules such as interleukin 4, which can pass into the brain.”

The findings suggest the possibility that treatments targeting the immune system might someday help ease some forms of autism, he concludes.

Implications for future treatments
“Research such as Dr. Filiano’s is important for revealing the precise molecular and cellular pathways through which the immune system influences the brain and behavior,” comments developmental pediatrician Paul Wang, Autism Speaks senior vice president for medical research. “These insights are necessary before researchers can design immune-modulating treatments that may improve brain function and behavior.”

Adds Dr. Filiano: “Clearly we first need to identify biomarkers that can help us understand how autism arises in different people. For some, there may be this immune component. For others, we may be looking at various genetic mutations or abnormalities in synaptic proteins. In each case, therapies may be different.”

Read more coverage of autism research at Neuroscience 2014 here.

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