A mind-altering microbe?

Posted on April 16, 2014   by Ruth Paget

Can a parasite change our behaviour? Might your mood today have been altered by a foreign organism living inside you, hiding from your immune system? Today at the Society for General Microbiology Annual Conference, Professor Joanne Webster, from Imperial College London, will be talking about the impact of Toxoplasma gondii.

Relationships between parasites and their hosts are complex and often multi-step. T. gondii is a protozoan parasite that causes toxoplasmosis. It can infect all warm-blooded animals, including people, but can only sexually reproduce in cats. If you were infected with T. gondii you probably don’t know it – initial symptoms in humans are often mild and shortlived. You probably won’t know if your cat has it either – they generally won’t seem unwell if they are infected.

Webster and her team primarily observed rats infected with T. gondii, looking at how attracted they were to cat urine. Usually, rats are scared of cats – if they smell cat urine they run a mile. Being near cat urine means you’re more likely to be near an actual cat, which in turn means you’ve more chance of being eaten. However, the team found rats infected with T. gondii showed very different behaviour and were highly attracted to cat urine. This behaviour is advantageous for the parasite – if an infected rat is eaten the parasite has a better chance of transferring to its final host, the cat, where it can complete its lifecyle. The researchers observed subtle changes in the rats’ behaviour that could increase the chances of predation – they were more active, more exploratory, more risk-taking.

What causes this unexpected change of behaviour became the focus of their research. Webster and colleagues found that the T. gondii parasite seems to be producing its own dopamine, a neurotransmitter released by brain cells. In one of the stages of its lifecycle T. gondii can be found in the brain of rats; could the parasite’s dopamine production be affecting the rats’ brain chemistry, changing their behaviour?

After her initial findings on rats, Webster is progressing her research, with funding from the Stanley Medical Research Institute, to understand the role T. gondii plays in some people with the mental health condition schizophrenia. Schizophrenia is a multi-faceted psychotic disorder that affects, among other aspects, a person’s view of reality. People with the condition can have strange thoughts, hallucinations and delusions and see or hear things that are not perceived by others. Dopamine levels are often altered in patients with schizophrenia, and medicines to treat schizophrenia, such as antipsychotics, target this dopamine system to help alleviate these symptoms.

A German group1 has showed that people with schizophrenia have much higher levels of antibodies for Toxoplasma in their blood than control groups who don’t have schizophrenia. People with schizophrenia who had received drug therapy in the past had lower antibody levels – if they were undergoing current treatment the levels were lower still.

A group from John Hopkins University2 showed that the mood stabilisers used to treat schizophrenia have antiparasitic effects, and they prevent replication of the T. gondii in vitro. Likewise, Webster and her group showed that T. gondii-infected rats treated with the same antipsychotic or mood stabiliser drugs did not develop the altered behavioural profile as seen in untreated rats, nor was there the same level of the parasite found within the brains of these drug-treated infected rats compared to controls. The results highlight that more research is needed to test and find out how the antipsychotic and mood stabilizing activity of some medications inhibits T. gondii replication in the brain, and what this effect is on infected individuals.

Research has shown that we see these very subtle changes in latently infected humans as those seen in rats studied by Webster’s group. Another team, have found that you are 2.58 times more likely to be involved in a traffic accident if a person is sero-positive for toxoplasma parasites. A number of studies have also replicated this finding. This may be due to decreased tentativeness or increased risk-taking behaviour.

Today Professor Webster will talk about her work, together with collaborators from Leeds, which aims to understand the role of parasite-produced dopamine in T. gondii-altered host behaviour. While their work is ongoing, it appears there are in fact multiple mechanistic routes involved in parasite manipulation of host behaviour.

The most common route of transmission of T. gondii to people is Toxoplasma cysts accidentally eaten in undercooked meat. Webster’s group have been able to prevent the development of behavioural alterations developing in infected rats through treating the early invasive stages of the parasite, but this will be more difficult in humans as it generally isn’t clear to an individual when a person first gets infected with T. gondii and it is generally mild and may be passed off as something else. At the moment we have few, if any, successful drugs active against the latter more resistant cyst stage of the parasite. Moreover, research3 seems to suggest the behaviour changes associated with sero-positivity become hard-wired in people, and it may be hard to reverse the behavioural changes if they have already developed even if you get rid of the parasite.

All these findings are important to Professor Webster’s continued research. With a better understanding of  T. gondii and how it affects rat behaviour, we may gain a deeper knowledge of the causes of some cases of human schizophrenia.

References

1. Leweke FM, Gerth CW, Koethe D, Klosterkötter J, Ruslanova I, Krivogorsky B, Torrey EF, Yolken RH (2004). Antibodies to infectious agents in individuals with recent onset schizophrenia. European Archives of Psychiatry and Clinical Neurosciences. 254:4-8.
2. Jones-Brando L, Torrey F, Yolken R (2003). Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii. Schizophrenia Research62:237-244.
3. 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. 18;8(9):e75246.