Toxoplasma gondii puts out a strange kind of mind control on rodents: When infected with this brain parasite, they seem to lose their fear of cats. When they are eaten, the microbe makes its way into the cats intestine to reproduce. However a new study argues that T. gondii’s effects on rodents aren’t cat-specific; instead, the parasite simply makes mice more eager to explore and less fearful of any species that might gobble them up, therefore, removing their sense of ‘fear’.
“It doesn’t make the parasite look to be this genius that many people thought it was,” says William Sullivan, a microbiologist at the Indiana University School of Medicine, Indianapolis, who was not involved in the new work.
T. gondii is able to infect any warm-blooded vertebrate, including people, but its relationship with cats unique. Only when in the feline gut can it reproduce sexually and assume a resilient, infectious form called an oocyst, which gets excreted to further spread the parasite.
Some researchers suspect the parasite makes a few slight changes rodent’s brain to change how it sees cats. And some lab tests have proved to of shown that mice would explore cat urine over that of other potential predators.
But that’s not what parasitologist Dominique Soldati-Favre at the University of Geneva discovered. When she and colleagues allowed T. gondii-infected mice to explore rooms containing four scents—those of themselves, bobcats, foxes, and guinea pigs (a nonpredator)—the rodents didn’t give the bobcat scent unique treatment. Indeed, infected mice spent the most time investigating the guinea pig and fox smells, the team concludes today in Cell Reports. The mice were also willing to explore a chamber containing a live, anaesthetized rat (another potential predator), whereas uninfected control mice almost invariably avoided the rat.
In many other behavioural tests, the team concluded that infected mice showed lessened anxiety and a more visible tendency to explore. For example, they spent more time in the arms of a maze that were open and exposed—areas that mice typically find threatening.
“We realized it wasn’t just about having lost fear against the cat,” Soldati-Favre says. “Really, these mice are very open-minded, and they go everywhere.”
Similar studies have concluded similar tweaks in anxiety and exploration, notes Joanne Webster, a parasitologist at the Royal Veterinary College, Hawkshead, who was not connected to the work. And the new research hasn’t convinced her that the cat-focused effect of T. gondii is a myth. “I don’t think they’ve got the power to dispute that here.” The researchers, she notes, report the odor preferences of the mice over 10 minutes, whereas some previous odor tests have tracked mice for several hours. She suspects the new test was too short to pick up a subtle tendency to explore the bobcat odour more intently than the others.
Many other experts embrace the new finding. T. gondii “clearly manipulates the crap out of the host,” says Laura Knoll, a parasitologist at the University of Wisconsin, Madison, and there’s no evolutionary reason this manipulation needs to focus on cats. Sexual reproduction may depend on the cat, but the parasite is transmitted any time an animal eats infected prey. A generally bold, curious mouse is “more likely to be out and about and get eaten. And every time it’s eaten—whether it’s [by] a fox or a bobcat—[T. gondii] does get passed on.”
Knoll’s team recently published a method to get T. gondii to reproduce in laboratory mice. Like that study, she says, this new one supports the idea that “there’s nothing that special about the cat.”
Soldati-Favre and colleagues propose that an immune response provoked by T. gondii cysts in the brain underlies the behavior changes. Unlike some previous studies suggesting the cysts concentrate in particular regions and may act on specific brain circuits, this one finds a roughly even distribution of cysts across the mouse cortex—the brain’s outer layer. And genetic analysis of brain tissue revealed certain markers of inflammation. Both cyst number and level of inflammation correlated with the degree of behavior change in infected mice, they report.
Up to one-third of humans are thought to harbour a T. gondii infection, known as toxoplasmosis, and similar research has linked it to schizophrenia and other mental illness. Soldati-Favre speculates that, because the parasite seems to produce fewer and smaller cysts in healthy humans than in mice, it may drive less inflammation and very minor behavioural change in people. The authors propose future studies to test whether infected humans show signs of inflammation, which is thought to contribute to certain neurodegenerative diseases.
If researchers ever decide they do want to combat the effect of T. gondii infection in the human brain, the new results suggest reducing inflammation might help, Sullivan says. His team recently found that dosing T. gondii-infected mice with an anti-inflammatory drug could reverse some of their behavioural changes.
The new results suggest the parasite has found a “sweet spot,” he says: invading the brain enough to provoke an immune response that drives the animal toward predators, but not enough to kill its host right away. It may not be an ultraprecise tweak to the perception of cats, but it’s still “a very smart strategy,” he says. “In a way, that is kind of mad genius.”