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An immune molecule that helps defend people from infection with viruses or bacteria may also keep brain activity in check, allowing people to be social. The preliminary findings, presented today at the 2015 Society for Neuroscience annual meeting in Chicago, show that brain exposure to interferon-gamma — a molecule released in response to infection — is necessary for normal social behavior in mice.
The findings add an intriguing new layer to the link between the immune system and the brain. They suggest that conditions characterized by social deficits, such as autism, could stem in part from a faulty immune system, says lead researcher Jonathan Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.
“We are showing a very clear immune molecule that is important for immune function and that also works in the brain on social behavior,” Kipnis says. “We’re leaving behind the perception that the brain and immune system are completely separate and [that] neuroscience is for neuroscientists and immunology for immunologists.”
The new findings follow from data presented at the same conference last year showing social deficits in mice that lack T cells — white blood cells that help the body fight off infection. Unlike normal mice, these so-called SCID mice show little interest in investigating another mouse in their cage. Restoring healthy T cells in the SCID mice reverses this behavior.
The SCID mice also have overactive connections among neurons in their prefrontal cortex, a region involved in complex cognitive tasks such as thinking and planning. Studies have shown this same hyperconnectivity in children with autism.
How T cells might affect the brain is somewhat of a puzzle, as they do not come into direct contact with neurons, notes Tony Filiano, a postdoc in Kipnis’ lab who presented the findings. T cells accumulate in the meninges, the thin layer of spinal fluid that protects the brain. The researchers looked in the meninges of mice they had previously tested for social behavior and found that the number of T cells there tracks with the mice’s level of social interest.
The researchers then turned their focus to interferon-gamma, a key molecule released by T cells. Mice that don’t produce this molecule are similar to SCID mice: They are antisocial and have hyperconnected brains, the researchers found. Blocking the molecule’s ability to penetrate the brain also dampens a mouse’s social interest.
Filiano and his colleagues genetically engineered mice that lack the receptors for interferon-gamma specifically in neurons in the prefrontal cortex. These otherwise normal mice once again show little interest in socializing with their cage-mates.
The researchers then turned to what the molecule might be doing in the brain. They found that injecting interferon-gamma into the spinal fluid in mouse brains boosts the activity of neurons in the prefrontal cortex that dampen brain activity. Mice with excess interferon-gamma are also resistant to chemically induced seizures. These findings suggest that interferon-gamma works like a circuit resistor — boosting inhibition to keep brain signals in check in the prefrontal cortex, says Filiano.
That the same molecule might work to fight off infection and induce people to be more social may not be as surprising as it seems at first glance. Over the course of evolution, once animals started gathering in large groups they would have also needed a way to ward off contagious infections, says Filiano. “When organisms aggregate, there’s a better chance they could spread virus,” he says. “It’s just a hypothesis at this point, but it could be pretty interesting if there’s co-evolution between social behavior and an antiviral response.”
For more reports from the 2015 Society for Neuroscience annual meeting, please click here.