Written by Mariana Mastache-Maldonado
Mind control and some history
We have all heard at some point in our lives about parasites: small beings (sometimes visible and sometimes not) who use a hospital for subsistence. There are different types: from those relatively common as lice, to the hallucinatory mushrooms of the genus Cordyceps that star in the series The Last of Us.
These fungi earned an important place within pop culture because of the interesting way they parasitize: They completely drain nutrients from their host (which are usually ants or spiders) before filling their body with spores that will allow the fungus to reproduce. Then, they force the insect to look for height and stay there, with the jaw buried in a leaf, and then emerge as an antenna from the head of the insect - already dead - and thus expel these spores, infecting other nearby insects in the process. This strategy that exhibits the fungus to spread has attracted the attention of many since it seems that Cordyceps exercised some type of “mind control” and/or zombification of the insect.
I'm often asked if what happens in the series can happen in humans as well. Although my answer is no, I can't help but think of another parasite that exerts control over its hosts: Toxoplasma gondii. This parasite is not a fungus, but a microscopic organism known as a protozoan, which is classified in the kingdom Protozoa.
While many protozoa play an important role in their ecosystems, such as breaking down organic matter and serving as food for other organisms, others can be harmful and cause disease in humans. Some examples of harmful protozoa include those responsible for diseases such as malaria, amoebic dysentery, and giardiasis.
Toxoplasma gondii. Image credit: https://commons.wikimedia.org/wiki/File:Toxoplasma_gondii_(2).jpg.
Toxoplasma gondii is a parasite that can infect humans and animals. It was discovered in 1908 and named a year later, but its medical importance was not recognized until 1939 when it was identified in tissues of a congenitally infected baby. In 1970 its life cycle was elucidated and it was discovered that humans are only intermediate hosts and that T. gondii needs to infect felines to reproduce sexually. Therefore, cats are fundamental in the replication of the parasite.
When someone becomes infected, they may develop a condition called toxoplasmosis. Despite being relatively common, it is not always well known or understood, so it is important to learn more about this parasite and its scopes.
Toxoplasmosis, what is it? How do we acquire it?
In most cases, people infected with toxoplasmosis do not have symptoms or mild flu-like symptoms, such as fever, headache, and fatigue. If no symptoms Toxoplasma remains in the body, inactive. This often gives lifelong immunity, so if there is exposure to the parasite again, the immune system removes it. However, in people with weakened immune systems, such as HIV patients, toxoplasmosis can lead to serious problems such as inflammation of the brain and other organs. It can also pose a significant risk to pregnant women and unborn babies. If a woman becomes infected during pregnancy, the disease can be transmitted to the fetus.
Transmission of toxoplasmosis can occur in several ways. In humans, the infection is usually acquired by ingesting food or water contaminated with cat feces infected with the parasite. It can also be through contaminated soil, especially if you put your hand to your mouth after contact, as well as by ingesting raw or undercooked meat.
And in our brain what happens?
When Toxoplasma manages to infiltrate the brain, overcoming physical obstacles in its path, it uses endothelial cells as a gateway. Once inside neurons, it forms structures known as cysts. These cysts are highly resistant and difficult to remove, and are not limited only to the brain, but can also form in various tissues of the body. These cysts play a crucial role in transmitting the parasite to new hosts and can evade both the immune response and medications. It should be noted that, in addition to neurons, astrocytes, and microglia cells can also be infected by this parasite.
Toxoplasma gondii cyst in mouse brain tissue. Image credit: https://commons.wikimedia.org/wiki/File:Toxoplasma_gondii_tissue_cyst_in_mouse_brain.jpg.
Although normally our immune system can control the presence of the parasite without doing damage, sometimes its appearance can trigger an inflammatory response that alters the communication between neurons. This process can increase the risk of experiencing seizures, muscle weakness, headaches, and confusion. For example, seizures can result from an imbalance in neurotransmitter transmission, with increased neuronal inhibition and decreased arousal, making the brain more prone to seizures. In severe cases, brain inflammation can cause irreversible damage.
But that's not all this parasite can do to our nervous system. It has been proven that T. gondii in its cyst state can “manipulate” the behavior of its host, suggesting that it may have a major impact on him. As the parasite needs to infect the felines (its definitive host), any factor that increases the likelihood that the intermediate host will be preyed upon by the feline is favorable for Toxoplasma. This coincides with several studies describing how infected mice begin to display risky behaviors, such as attraction to urine and/or loss of fear of cat odors. Behaviors like this have also been observed in species such as wolves. An investigation was conducted in 2022 by Meyer and collaborators where they studied gray wolves and pumas in Yellowstone National Park. They found that wolves that shared territory with pumas (which are the definitive host for Toxoplasma gondii in that area) were more likely to be infected. In addition, infected wolves made riskier decisions, such as dispersing and becoming pack leaders. This could create a cycle where wolves and pumas transmit the disease and even compete more with each other. These findings demonstrate that these parasites can have important effects on animals, beyond simply making them sick, and this can affect groups and even the ecosystem itself.
For zombie fans, these parasite-altered behaviors might already remind them of more than one series.
It is important to note that in urban environments we are not intermediate hosts for the parasite to reproduce (as could happen with large cats in open natural areas). However, we can still accidentally become infected and experience certain effects on our behavior. In humans, the infection has been linked to some neurological and psychiatric disorders, such as schizophrenia and even suicide attempts. Other studies have shown an association between driving rabies and the presence of T. gondii. In addition, an increase in testosterone has been found in infected men, which has been associated with increased impulsivity, aggression, and risk-taking behavior.
Zombies or altered neurotransmission? All you need to know.
Under the idea that Toxoplasma manipulates the behavior of its host, it is common to wonder if it could turn us into “consummate zombies.” However - which might disappoint fans of games and series like The Last of Us or The Walking Dead - the answer is no.
However, neuroscience has found interesting clues about the changes in decision-making seen in hosts with toxoplasmosis. Infection with the parasite causes certain genes in the brain to change, specifically in an area called the amygdala, which plays a crucial role in processing emotions (particularly fear and anxiety). This gene modification is called demethylation and changes the way circuits in the brain that are associated with fear (also known as dopaminergic circuits) work.
Within the exciting field of science, there is a fascinating branch known as epigenetics. Simply put, epigenetics refers to changes in the expression of our genes without altering their DNA sequence. Now, one of the intriguing epigenetic processes is demethylation, which can have a significant impact on brain functioning. Importantly, demethylation is one of the ways a parasite can influence the brain, altering behavior or overall health.
Epigenetic regulation does not end there for Toxoplasma. It is known, for example, that when it invades the host body, it can affect the immune system by suppressing the expression of about 71 of its genes. This allows the parasite to persist in the body.
In addition to dopamine, other neurotransmitters such as serotonin and glutamate may also play a role in T. gondii-induced behavioral changes. Take for example rodents that manifest risky behaviors, in studies that investigate the neurological basis of anxiety they have used as a model the reaction of possible prey to cat stimuli. In them, it has been found that blocking receptors in the brain, such as NMDA (normally anxiogenic in the amygdala) and/or serotonin (5-HT) causes rats to approach cats or their odors “without fear.”
Preventing Toxoplasmosis: The Importance of Education
Even though most infected people experience no symptoms or only mild symptoms that go away within a few weeks, it is important to take preventive measures to avoid infection. Hygiene remains the best preventive measure as there is currently no vaccine to prevent toxoplasmosis in humans.
It is advisable to wash your hands, and cooking utensils, and cook the meat properly. Pregnant women should avoid contact with cats and their litter box, or wear gloves and wash their hands after handling the litter box. In addition, you should avoid ingesting untreated water and wash fruits and vegetables well before consuming them.
Toxoplasmosis is a public health problem that affects both humans and animals. For this reason, it is important to educate and raise awareness of the erroneous myths that often arise around this disease. Education can help reduce the overall incidence of infection, which in turn can lessen the burden on healthcare systems.
Importantly, early detection of Toxoplasma gondii infection can lead to prompt treatment and better results in its management. Therefore, it is essential to be attentive to the symptoms and go to the doctor in case of presenting them.
Further research is required to better understand the relationship between Toxoplasma gondii infection and the human brain.It is necessary to understand the mechanisms by which the parasite can affect it and develop specific treatments that address the impact of the infection.This parasite is highly prevalent in both human and animal populations and has a predilection for the central nervous system, making it an important research topic that should not be ignored.
References:
Emese Prandovszky, Gaskell, E. A., Martin, H., Dubey, J. P., Webster, J. P., & McConkey, G. A. (2011). The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism. 6(9), e23866–e23866. https://doi.org/10.1371/journal.pone.0023866.
Meyer, C. J., Cassidy, K. A., Stahler, E. E., Brandell, E. E., Anton, C. B., Stahler, D. R., & Smith, D. W. (2022). Parasitic infection increases risk-taking in a social, intermediate carnivorous host. 5(1). https://doi.org/10.1038/s42003-022-04122-0.
Thibaut Desmettre. (2020). Toxoplasmosis and behavioral changes. 43(3), e89–e93. https://doi.org/10.1016/j.jfo.2020.01.001.
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