Monkeys exposed in utero to their mother’s immune response to a mock infection show inflammation in their brains four years later, similar to which can be associated with schizophrenia and autism. Melissa Bauman presented new findings in her research in brain inflammation in monkeys at the 2014 Society for Neuroscience annual meeting in Washington DC, November 14, 2014.
Infections during pregnancy have long been known to increase a woman’s odds of having a child with schizophrenia or autism. In the past few years, researchers have confirmed in mouse models that a mother’s immune response can lead to a wide array of symptoms in her pups, such as anxiety, repetitive burying of marbles, and abnormal vocalizations and social interactions.
However humans are not similar to mice in their behavior and social interactions, but are similar to monkeys.
“There are limitations in relying solely on rodent models to evaluate risk factors for complex disorders such as autism,” says Melissa Bauman, Ph.D., CNPRC Affiliate Scientist and assistant professor of psychiatry and behavioral sciences at the University of California, Davis.
Dr. Bauman and her colleagues developed a macaque model of maternal immune activation at the CNPRC: They injected pregnant monkeys with a mock flu virus at the end of either the first trimester or the second. Both groups of young macaques show stereotyped and repetitive movements by age 2, the study found. Babies exposed during the first trimester also show abnormal social behaviors.
“I was surprised how consistently affected the first-trimester animals were,” Bauman says, especially because primate models, unlike mice, are not genetically identical and therefore more of a true representation of the variety in human populations.
The new study investigated the brain activity of the monkeys at four years old, their age of puberty. These experiments relied on a noninvasive imaging technology called positron emission tomography, or PET, in which radioactive tracers travel from the animals’ blood to their brains and bind to specific proteins.
Bauman’s team used a tracer called PK11195, which binds to activated microglia, cells associated with brain inflammation that have been linked to autism. Monkeys exposed to an infection in either the first or second trimester show abnormally high levels of inflammation across the whole brain, the study found.
In another experiment, the researchers turned to a tracer called FMT, which is a marker of the synthesis of dopamine, a chemical messenger. Increased levels of dopamine in the striatum, a deep brain region involved in planning and movement, are associated with schizophrenia.
The new study found that the brains of the monkeys exposed to maternal infection in the first or second trimester show higher levels of striatal dopamine than in controls.
“We’re pretty excited by these data,” Bauman says. The monkey models “are a nice way to bridge the gap between rodent models and clinical populations.”
However, it is important to remember that not all women who experience infection during pregnancy go on to have a child with altered neurodevelopment. Animal models are essential to determine which women and which gestational time points are most vulnerable.
What these data don’t yet explain, however, is why exposure during the first trimester, but not the second, leads to social problems reminiscent of autism. “At this point, we’re still searching,” Bauman says.