Toxoplasma-infected mice remain unafraid of cats even after parasite clearance

Sep 18, 2013
Even after infection with Toxoplasma has been removed from rodents' brains, they continue to behave as if unafraid of the smell of cat urine, suggesting that the infection causes long-term changes in the brain. Credit: Wendy Ingram and Adrienne Greene

Chronic infection with the parasite Toxoplasma gondii can make mice lose their innate, hard-wired fear of cats. This loss of their innate fear may persist after the parasite is no longer detectable in their brains, suggesting that initial infection may cause permanent changes in the mechanisms underlying their fear of predators. The results are published September 18 in the open access journal PLOS ONE by Wendy Ingram and colleagues from the University of California, Berkeley.

The Toxoplasma parasite can be deadly, causing spontaneous abortion in pregnant women or killing immune-compromised patients, but it has even stranger effects in mice.

Infected mice lose their fear of cats, which is good for both cats and the parasite, because the cat gets an easy meal and the parasite gets into the cat's intestinal track, the only place it can sexually reproduce and continue its cycle of infection.

New research by graduate student Wendy Ingram at the University of California, Berkeley, reveals a scary twist to this scenario: the parasite's effect seem to be permanent. The fearless behavior in mice persists long after the mouse recovers from the flu-like symptoms of toxoplasmosis, and for months after the parasitic infection is cleared from the body, according to research published today (Sept. 18) in the journal PLOS ONE.

"Even when the parasite is cleared and it's no longer in the brains of the animals, some kind of permanent long-term behavior change has occurred, even though we don't know what the actual mechanism is," Ingram said. She speculated that the parasite could damage the smell center of the brain so that the odor of cat urine can't be detected. The parasite could also directly alter neurons involved in memory and learning, or it could trigger a damaging host response, as in many human autoimmune diseases.

Ingram became interested in the protozoan parasite, Toxoplasma gondii, after reading about its behavior-altering effects in mice and rats and possible implications for its common host, the domesticated cat, and even humans. One-third of people around the world have been infected with Toxoplasma and probably have dormant cysts in their brains. Kept in check by the body's immune system, these cysts sometimes revive in immune-compromised people, leading to death, and some preliminary studies suggest that chronic infection may be linked to schizophrenia or suicidal behavior.

Researchers found that mice's lack of fear of cats persisted even when inflammation markers or cysts could not be detected in mice. Credit: Wendy Ingram and Adrienne Greene

Pregnant women are already warned to steer clear of kitty litter, since the parasite is passed through cat feces and can cause blindness or death in the fetus. One main source of spread is undercooked pork, Ingram said.

With the help of Michael Eisen and Ellen Robey, UC Berkeley professors of molecular and cell biology, Ingram set out three years ago to discover how Toxoplasma affects mice's hard-wired fear of cats. She tested mice by seeing whether they avoided bobcat urine, which is normal behavior, versus rabbit urine, to which mice don't react. While earlier studies showed that mice lose their fear of bobcat urine for a few weeks after infection, Ingram showed that the three most common strains of Toxoplasma gondii make mice less fearful of cats for at least four months.

Using a genetically altered strain of Toxoplasma that is not able to form cysts and thus is unable to cause chronic infections in the brain, she demonstrated that the effect persisted for four months even after the mice completely cleared the microbe from their bodies. She is now looking at how the mouse immune system attacks the parasite to see whether the host's response to the infection is the culprit.

"This would seem to refute – or at least make less likely – models in which the behavior effects are the result of direct physical action of parasites on specific parts of the brain," Eisen wrote in a blog post about the research.

"The idea that this parasite knows more about our brains than we do, and has the ability to exert desired change in complicated rodent behavior, is absolutely fascinating," Ingram said. "Toxoplasma has done a phenomenal job of figuring out mammalian brains in order to enhance its transmission through a complicated life cycle."

Explore further: Male monkey filmed caring for dying mate (w/ Video)

More information: Ingram WM, Goodrich LM, Robey EA, Eisen MB (2013) Mice Infected with Low-Virulence Strains of Toxoplasma gondii Lose Their Innate Aversion to Cat Urine, Even after Extensive Parasite Clearance. PLoS ONE 8(9): e75246. DOI: 10.1371/journal.pone.0075246

Related Stories

Brain parasite directly alters brain chemistry

Nov 04, 2011

A research group from the University of Leeds has shown that infection by the brain parasite Toxoplasma gondii, found in 10-20 per cent of the UK's population, directly affects the production of dopamine, a key chemical messen ...

Study turns parasite invasion theory on its head

Dec 23, 2012

Current thinking on how the Toxoplasma gondii parasite invades its host is incorrect, according to a study published today in Nature Methods describing a new technique to knock out genes. The findings coul ...

Feline friends?

Sep 07, 2012

A report showing that 350,000 people in the UK become infected with the Toxoplasma parasite each year has raised new concerns about its risks and has prompted a rethink of the dangers posed by cats.

Recommended for you

Male monkey filmed caring for dying mate (w/ Video)

20 hours ago

(Phys.org) —The incident was captured by Dr Bruna Bezerra and colleagues in the Atlantic Forest in the Northeast of Brazil.  Dr Bezerra is a Research Associate at the University of Bristol and a Professor ...

Orchid named after UC Riverside researcher

Apr 17, 2014

One day about eight years ago, Katia Silvera, a postdoctoral scholar at the University of California, Riverside, and her father were on a field trip in a mountainous area in central Panama when they stumbled ...

In sex-reversed cave insects, females have the penises

Apr 17, 2014

Researchers reporting in the Cell Press journal Current Biology on April 17 have discovered little-known cave insects with rather novel sex lives. The Brazilian insects, which represent four distinct but re ...

Fear of the cuckoo mafia

Apr 17, 2014

If a restaurant owner fails to pay the protection money demanded of him, he can expect his premises to be trashed. Warnings like these are seldom required, however, as fear of the consequences is enough to ...

User comments : 2

Adjust slider to filter visible comments by rank

Display comments: newest first

Birger
2.3 / 5 (3) Sep 19, 2013
Less fearful of cats? Having grown weary of the anti-science attitude of Tea Party politicians, I suggest spraying them with Toxoplasma Gondii and sending them on tiger safaris in Asia...
Gmr
2.3 / 5 (3) Sep 19, 2013
@Birger - no on trying to get somebody killed, but I wonder if removing a primal fear response might not demotivate some relatively conservative attitudes. Implications on all sides for politics; it's been shown conservativism is related to heightened fear response and lessened impetus to novelty; conversely, somebody is going to say it's proof that liberal and progressive thought is due to parasite contamination and subsequent brain damage.

What to do. Hmm.

More news stories

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Male monkey filmed caring for dying mate (w/ Video)

(Phys.org) —The incident was captured by Dr Bruna Bezerra and colleagues in the Atlantic Forest in the Northeast of Brazil.  Dr Bezerra is a Research Associate at the University of Bristol and a Professor ...

Researchers develop new model of cellular movement

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

Impact glass stores biodata for millions of years

(Phys.org) —Bits of plant life encapsulated in molten glass by asteroid and comet impacts millions of years ago give geologists information about climate and life forms on the ancient Earth. Scientists ...