How This Cat Parasite Can Affect Our Brain Neurochemistry


When parasitology and neurobiology intersect.
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Lingering in the Brain

Toxoplasma gondii has infected nearly one in three people worldwide. Cats are the only host wherein T. gondii can reproduce cysts. About 40% of cats in the United States are estimated to carry T. gondii cysts. And this parasite is most famous for flipping the instincts of infected rodents to find the smell of cat urine alluring. T. gondii soon received its title as a brain-altering parasite.

T. gondii cysts in the cat feces, uncooked meat, or other contaminated food/water can be accidentally ingested by warm-blooded creatures. The cysts then translocate across the intestinal barrier and integrate themselves into the muscle and brain tissues permanently.

The cysts, however, rarely cause diseases owing to the works of a proper immune system. Under conditions of a weakened immune system, toxoplasmosis can occur. Symptoms include inflamed heart, lungs, eye, and brain, swollen lymph nodes, fever, and muscle aches.

For most of us, toxoplasmosis is mild with just flu-like symptoms that usually disappear after a few weeks on their own. But the parasite persists in the human muscle and brain tissues and reactivates again when the time is right. The immune system, unfortunately, just doesn’t know how to eliminate T. gondii completely.

T. gondii is absorbed by humans via digestion, enters the bloodstream and also migrates into the brain to get into nerve cells for the rest of one’s life,” explains the neurobiologist Karl-Heinz Smalla from the Leibniz Institute for Neurobiology, Germany.
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Messing Up the Brain Neurochemistry

The consequences are deeper than just mild toxoplasmosis. Scientists across the world have found the intriguing link between latent T. gondii infection and neurological disorders and symptoms like bipolar depression, schizophrenia, suicidality, aggression, impulsivity, Alzheimer’s disease, and brain cancers.

“Humans are accidental hosts to T. gondii and the parasite could end up anywhere in the brain, so human symptoms of toxoplasmosis infection may depend on where the parasite ends up. This may explain the observed statistical link between incidences of schizophrenia and toxoplasmosis infection,” explains the parasitologist Glenn McConkey from the University of Leeds, England.

In other words, which neuropsychiatric disorder caused by T. gondii may depend on which brain cells the parasite enters. And the latent parasite must have done something to the brain cells when it reactivates from time to time.


McConkey’s research focused on how T. gondii manipulates neurons to produce dopamine. His team showed that infected neurons ramped up their metabolism of dopamine — synthesizing and releasing dopamine at 3-times the normal amount of uninfected neurons. They later found that T. gondii cysts in brain tissues contain an active dopamine-synthesizing enzyme called tyrosine hydroxylase.


In a 2018 study, a team of German scientists created a mouse model of latent T. gondii infection. Using state-of-the-art proteomic techniques, they showed that neurons that produce glutamate became inactive in infected mice. These glutaminergic neurons are those involved in learning and neuroplasticity. The antiparasitic agent, sulfadiazine prevented this but large numbers of T. gondii cysts remained in the brain. ↑

Gamma-aminobutyric acid (GABA)

T. gondii exploits the GABA neurocircuitry of dendritic cells — a type of immune cell. Infected dendritic cells secrete more GABA than their normal counterparts. GABA is an inhibitory neurotransmitter and it inhibits the activity of dendritic cells. By treating infected mice with agents that block GABA release, T. gondii replicated 2.8 times less than untreated mice.

“For toxoplasma to make cells in the immune defense secrete GABA was as surprising as it was unexpected and is very clever of the parasite,” commented Antonio Barragan from the Swedish Institute for Communicable Disease.

A recent 2019 paper revealed the same for microglia — macrophages in the brain — wherein T. gondii made the microglia secrete more GABA. The parasite, therefore, thwarts the microglia and dendritic cells away as it spreads in the brain.

↓ Serotonin

T. gondii doesn’t manipulate serotonin directly, per se. Chronic neuroinflammation induced by the parasite activates the IDO enzymatic pathway that depletes tryptophan and serotonin in the brain. This is a common mechanism shared by brain infections, which may explain why infected individuals commonly develop depressive-like behaviors regardless of the pathogen involved.
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The Bigger Picture

The links between T. gondii and a panoply of neurological disorders are not always apparent in all epidemiological studies. This means that T. gondii is not a definite risk factor — like smoking and lung cancer — that causes brain disorders by itself.

It probably compounds with other genetic and environmental risk factors to ultimately determine if these neurological disorders develop, according to Robert H. Yolken, M.D. from Johns Hopkins University School of Medicine, specializing in infectious diseases and neuropsychiatric disorders.“We hypothesize that disease occurs in the presence of the relevant susceptibility genes, parasite genotype and other innate and environmental factors such as other infections, the microbiome, or stress that influence immune responses,” explains Huân M. Ngô et al. from University of Chicago, the United States in Nature Scientific Reports in 2019.

We know that pathogens preferentially infect certain cells or tissues. It made sense for some pathogens to love brain cells as well. While T. gondii is one, herpes simplex virus type 1 (HSV-1) is also another common example that likes to infect the hippocampus.

“It’s mind-boggling…to imagine that this complex, highly-evolved organ we call the human brain can be manipulated and turned dysfunctional by organisms that have a diameter on the scale of micrometers. It creates for us a strangely wonderful sense of impotence that causes us to step back and reassess the position of superiority we generally give ourselves over other organisms,” writes Marc Dingman, Ph.D.

This article was originally published in Microbial Instincts with minor modifications.

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