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'Mind-altering' parasite causes major changes in mouse brains

Toxoplasma gondii makes mice less anxious and more curious, but scientists are divided on exactly how it influences behavior.

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Has the myth of the mind-altering parasite been busted?

Jackson Ryan/CNET

There's a fairly good chance you're infected with a mind-altering parasite. And if not you... then maybe your cat. The parasite, known as Toxoplasma gondii, is one of the most prolific proliferators on the planet, with an ability to infect basically any warm-blooded animal. Scientists think it may have infected upward of 3 billion humans. 

But it's OK. There's no real reason to flip out -- it's mostly harmless. 

Toxoplasma is a remarkable single-celled organism in the same category as the malaria parasite and has long captured the imagination of researchers and the public because of its ability to change behaviors in both rodents and humans. Studies have shown that rodents infected with Toxoplasma are more fearless, and some researchers have connected infection in humans with impulsiveness and mental health conditions like schizophrenia.

In most warm-blooded mammals, the parasite is basically inert and forms protective cysts to survive, including in brain tissue. The cysts remain in the body for life, slumbering away within hosts -- unless they have a weakened immune system, in which case, Toxoplasma can be bad news.

In a cat's gut, it's a different story. That's where the parasite gets down to business. Toxoplasma's life goal is singular: Get inside a cat, mature and reproduce. Once the Toxoplasma "children" are born, the cat excretes them. And the cycle starts anew.

A Center for Disease Control and Prevention diagram of the Toxoplasma lifecycle.

CDC/DPDx

To get into the cat, the standing theory suggests Toxoplasma changes rodent behavior by using a form of "mind control." Instead of being repelled by cat odors or hiding, the rodents are more likely to face a feline. Toxoplasma seems to decrease anxiety and make the rodents more courageous. That increases their chances of being eaten, giving Toxoplasma the best chance to sneak inside its preferred host. 

The rodents are furry Trojan horses, bursting with a battalion of parasites waiting to get inside a cat.

However, intense scientific debate still surrounds Toxoplasma and the extent of its mind-altering capabilities. Studies have shown the organism does affect behavior in mice, but how the parasite achieves this remains unknown. Is it an adaptive mechanism spurred by evolution? Does it manipulate the host brain directly, bending it to its will? Or does the infection cause the host's immune response to go haywire, causing inflammation in the brain that leads to behavioral changes? 

New research, published in the journal Cell Reports on Tuesday, attempts to answer those questions. Researchers examined behavioral changes in mice as a result of Toxoplasma infection, subjecting the rodents to an array of behavioral tests to determine if they were less fearful of predator odors and open spaces. Then they dug into the brain, focusing their attention on parasitic cysts and genetic markers of inflammation, to determine if tangible physiological changes contributed to mice behavior. 

"There has been a lot of controversy around the question of whether general anxiety is lowered or not," says Ph.D. student Madlaina Boillat, a neurogeneticist at the University of Geneva and co-first author on the paper. "Studies have reported either no change in anxiety upon infection, increased anxiety or lowered anxiety, depending on variables such as the behavioral assay that was used and on infection level, which is highly dependent on mouse strain and parasite strain."

Cat scan

In one behavioral test, mice were placed in an X-shaped "maze." Two arms of the X were bordered by large walls and two arms were completely open. Non-infected mice usually stick to the arms containing border walls for safety, but mice infected with the parasite spent a lot more time exploring the open arms. Another test, Boillat explains, showed infected individuals were willing to sniff out fox and guinea pig odors just as readily.

This new finding is particularly important because it demonstrates the parasite does not selectively manipulate host behavior to be less fearful of cats as the so-called theory of "fatal attraction" suggests. The rodents don't perform a scan specifically seeking out cats. Instead, it appears the parasite likely tinkers with more generalized anxiety pathways in the brain and causing an increase in curiosity. 

The physiological response is telling.

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A Toxoplasma gondii cyst embedded in brain tissue.

CDC/DPDx

"Our RNA-sequencing experiment shows there are major changes occurring in the brain [of] infected mice," says Boillat. "Highly infected mice show signs of immunopathology, such as neuronal death and excitotoxicity."

The severity of these symptoms were related to how many ball-like cysts formed and how much inflammation was seen in mouse brains. It follows then that Toxoplasma doesn't directly mess with brain cells, somehow pulling the strings in a rodent's gray matter for its own benefit, but rather drives inflammation. This follows previous research that demonstrated a similar phenomenon: When cysts and inflammation increased, so did the activity level of infected mice. 

Rather than the (admittedly very cool) idea the parasite is performing some sort of mind control, it seems likely the immune response is driving the unusual -- and potentially fatal -- behaviors. Such a finding could have far-reaching implications if it holds up in humans, too. 

"It is known that an inflammation in the brain, whether it is induced by Toxoplasma gondii or other pathogens, can act as a trigger for mental illnesses in humans," Boillat notes. However, she suggests we should be "very cautious" in interpreting the results. The team observed strong correlations between infection, gene expression in the brain and behavior, but it cannot provide any causative explanations. 

Moreover, humans and mice respond differently to infection with the parasite, making it difficult to draw direct comparisons between species.

The team's next challenge is to understand how inflammation in the brain can drive behavioral changes in mice. Is it because brain cells are being overstimulated in some way, or are the molecular signals going haywire? Does the parasite's presence change the way the brain responds to stimuli? 

Answering those questions will shed further light on Toxoplasma's purported mind-control techniques and, as an aside, help me look at the neighborhood tabby with less dread. 

Originally published 8:15 a.m. PT.