Toxo on the Brain

Toxoplasma gondii is one of those parasites that, once you learn about what it's capable of, you can't get it out of your head.  In some cases, that could be taken literally.  To learn the basics about this parasite, see this previous post.  Did you read it? Good! Let's move on.

Since the early 90's, scientists have known that T. gondii causes drastic behavioral changes in rats and mice.  It represses the animals' innate fears by essentially screwing with their brain chemistry until they start to actually like the odor of cat urine rather than being afraid of the scent.  This behavioral change is believed to be instigated by the parasite in order to get it into the definitive host (a cat).

Those studies were vastly interesting, but in recent years scientists have begun to find correlations between  toxoplasmosis and changes in human behavior.  Therefore, we will focus on the research presented with regard to human manipulation as opposed to rodent manipulations for the purposes of this post.

The idea that Toxoplasma could actually affect human behavior was radical when first proposed by a Czech biologist named Jaroslav Flegr.  His work has been highly controversial among people within the scientific community, but his diligence has paid off.  In November of 2012, a group of Swedish researchers discovered that this parasite hijacks white blood cells in order to make its way to the brain. Back in 2009, U.K. scientists discovered that this parasite has two genes for making a precursor molecule for the production of dopamine (1-DOPA, in case you were wondering). Upon further testing, it was found that the parasite induces the upregulation of dopamine production once in the brain of rats, and later it was found that infected humans also have increased levels of this neurotransmitter.

A Pseudocyst of parasites that forms in the brain.

The significance of increased dopamine production is how dopamine affects our behaviors. It was noted in rats to affect male and female rats differently, something that is, again, reflected in infected humans. In men, the increase in dopamine leads to a decrease in the production of the stress-hormone known as cortisol. This causes a spike in testosterone levels, which can drastically change a man's personality. These changes include increased aggression, social difficulties, increased dominance, impulsiveness, and a disinterest in the feelings of others (often to the point of psychopathy).

The increased production of dopamine in females causes very different changes.  Women's bodies are more adapted to dealing with increases in dopamine levels.  To cope with this, a female's body releases an influx of the sex hormones oestrogen and progesterone into the dopamenergic systems.  Unlike in men, this causes an increase in cortisol production in females, which drops the already low levels of testosterone.  Infected women tend to be less impulsive, more sensitive to the needs of others, more motivated, more outgoing, and more relaxed.  However, they do seem to experience hair loss and lowered libido in response to infection.

The personality changes described above become more drastic over time. Regardless of gender, infected people have been shown by some of Flegr's studies to be almost twice as likely to be involved in a car accident.  This is because the parasite leads humans to having slower reaction times and increased fatigue.  Infected people have an increased risk of both suicide and of developing mental problems for which they will need to be institutionalized for their own safety.  There are also many links between toxoplasmosis and psycological disorders. Mood disorders such as bipolar disorder and clinical depression have been connected  with infection as has obsessive-compulsive disorder.

The disorder that has been most studied in connection with toxoplasmosis is schizophrenia.  Dopamine plays a big role in the development of schizophrenia.  Many people diagnosed with this disorder test positive for Toxoplasma gondii antibodies.  The link between schizophrenia and toxoplasmosis is still being studied, but it makes sense that an interplay could be present due to their connections with dopamine.

Toxoplasma gondii in green,
multipling inside a dendritic cell.

I mentioned earlier, it was recently discovered that the parasites hitch rides on white blood cells.  To be more specific, they grab hold of dendritic cells and use them to get into the host's brain. To get the dendritic cells to move, the parasites induce these cells to produce GABA (a neurotransmitter).  Like igniting a flame, the release of GABA by the dendritic cells excites GABA receptors outside the cell and sends it blasting through the body until it reaches the brain.  Another interesting thing about GABA? Changes in GABA levels are associated with psychiatric disorders such as...you guessed it...schizophrenia.

Now let's switch gears...we know that this tiny, single-celled protist may be the cause of some serious neurological disorders and that it induces some interesting changes in personality.  But this parasite isn't all bad, it has been reported that women infected with an asymptomatic form of toxoplasmosis (known as "latent toxoplasmosis") may benefit from the infection.  It seems that women infected with this prior to pregnancy are protected from contracting acute toxoplasmosis and their fetuses are protected from getting congenital toxoplasmosis! How cool is that?

It gets cooler!  Some scientists are doing cutting-edge research on using this parasite to TREAT neurological problems.  Yes, you read that right!  It seems that controlled infections can help people with problems relating to decreases in dopamine, such as ADD and ADHD.  It is also being used in researching treatments for both Parkinson's disease and Alzheimer's disease!

I guess that just goes to show you that there are two sides to every coin...or in this case, to every unicellular eukaryotic endoparasite! :p  With all of the advances being made in helminthic therapy, it will be great to see what medical science is able to do to utilize the manipulative capabilities of this parasite in the treatment of low-dopamine related disorders.

Who can resist posting rainbow pictures of parasites?!