UC Berkeley researcher shows parasite removes mice’s innate fear of cats

Wendy Ingram/Courtesy

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In the famous game of cat and mouse, new research suggests the playing field might not be entirely even.

Researchers found that a parasite, toxoplasma gondii, permanently affects the brains and behavioral patterns of rodents. The parasite removed mice’s innate aversion to and fear of cats even four months after the infection cleared.

“Who would have thought that parasites could make such an indelible impression — even after the infection is gone?” said Nilabh Shastri, a UC Berkeley professor of immunology and pathogenesis.

Though the parasite has been known to eliminate mice’s hardwired fear of cats, previous research involved only one strain of the parasite, Type II. Wendy Ingram, a doctoral candidate in the campus department of molecular and cell biology, set out to study the details of the parasite using a genetically modified Type I strain instead.

For the research, Ingram placed mice in small enclosures with a dish containing either bobcat or rabbit urine affixed to each end. Although mice usually avoid cat urine because it marks the predator’s territory, infected mice forgot this biological habit.

“When the parasite gets in the mouse brain, it finds neurons and goes in and hangs out, and the immune system has to be there so the parasite doesn’t kill the animal,” Ingram explained. “But when we looked at the brain, we couldn’t find any leukocytes (immune cells), which have to be there if there is a parasite there.”

In examining mice’s brains, researchers also saw a “bread-crumb trail” of where the parasite had been and how many cells the parasite had invaded by observing previously infected proteins that turned green in their scans.

“It was absolutely beautiful, shocking data that hundreds and hundreds of more neurons had turned green with no parasite in it,” Ingram said. “Figuring out what proteins are being injected could tell us a lot about which one of those could be the culprit.”

These findings could have far-reaching implications for the medical community, suggesting that curing an infection may not eradicate all symptoms, Ingram said. Using this protein-tracking notion, scientists can look at “biological imprints left behind” to better understand why certain symptoms arise in individuals with no diagnosable disease.

Many researchers in immunology also question the mechanism by which the loss of aversion originally takes place.

Because the parasite can sexually reproduce only in the feline stomach, its ability to extinguish fear in rodents may serve as a self-preservation technique, a possible evolutionary adaptation, according to the study.

“Fear is one of nature’s most ancient defense mechanisms,” Shastri said. ”Toxoplasma should therefore be considered at the very forefront to be able to mess up the fear mechanism.”

It is unknown precisely why the effects of the parasite linger after the infection is cured.

Kaoru Saijo, a researcher in the UC San Diego department of cellular and molecular medicine, said the parasite infection may cause “chronic and significant changes” in the immune system, leading to subsequent changes in behavior. Ingram will follow her study by investigating this possibility.

“This is all great work with totally unexpected results,” Shastri said. “Nature never ceases to amaze.”

Virgie Hoban covers research and ideas. Contact her at [email protected]