Thursday, 12 October 2017

Toxoplasma Gondii: Common Brain Parasite Behind Brain Disorders?

Most people have never heard of the brain parasite called Toxoplasma gondii. We tend to think that creatures of such kind belong to the realm of exotic tropical diseases affecting people somewhere in miasmatic swamps of equatorial jungles. However, toxoplasma infection is remarkably common: it is believed that one in every three persons around the world have it. And not only in tropical regions, the prevalence of this infection in France is estimated at 84%! In fact, T. gondii is one of the most common parasites in the developed world. The majority of people reading this article have it in their brains.

If the infection is so common, why is it hardly ever mentioned? The reason is simple. As horrible as it sounds to have a parasite living in your brain, the infection with Toxoplasma gondii is asymptomatic and doesn’t seem to affect us in any obvious way. The initial exposure to the parasite may cause some flu-like symptoms, but very soon the infection enters latent stages and does not manifest itself. It can, however, become dangerous in people with weakened immune system, such as those with HIV/AIDS.

The parasite has a rather curious life cycle. It can live in almost any warm-blooded animal, but its major hosts are cats and other felines. In their bodies, the parasite can sexually reproduce giving rise to new generations of offspring. In other animals, as well as in humans, Toxoplasma gondii can only reproduce asexually. Thus, feline species are the definite hosts of T. gondii, while humans can only be intermediate hosts.

The oocysts produced in cats get excreted with feces and spread in the environment. This is where they can be picked up by rats and mice. In these animals, the parasite eventually reaches the brain, and here is where something really unusual happens. The parasite modifies the behavior of the rodents, making them less afraid of the smell of cats.

In addition, the brain infection affects the motor ability of animals, thereby making them easier prey for cats. These behavioral changes are achieved by introducing some epigenetic modifications affecting key neurons regulating the above behavioral characteristics. The behavioral modification of the host increases the chances of the parasite getting into the body of cats, and thus increases the chances of its reproductive success.

The important question is: does the infection with Toxoplasma gondii change human behavior as well? It appears that the answer to this question is yes. The results of psychological testing published in 2007 demonstrated gender-dependent changes in the behavior of humans affected by toxoplasmosis. Infected men had a tendency to disregard rule and were more expedient, suspicious, and jealous. Infected women, however, were more warmhearted, conscientious, and moralistic. The gender differences are related to different levels of testosterone in men and women.

Motor functions also appear to be affected in infected people. One study demonstrated a 2.65 times higher chance of traffic accidents among people with latent toxoplasmosis. The antibodies to the parasite were detected more often among drivers who were involved in traffic accidents, as compared to the statistical average.

Furthermore, a number of reports demonstrated a correlation between toxoplasmosis and the incidence of schizophrenia and bipolar disorder. Several studies have shown that the risk of attempted suicide is also higher among people affected by latent T. gondii infection. Correlation does not necessarily imply that the infection is the causative factor of neurological disorders, but it is likely to be a risk factor in the development of these conditions.

It is important to mention here that not all researchers believe that T. gondii infection really affects human behavior or the risk of diseases to any significant degree. Some recently published studies indicate that these risks are very small, and the previously published correlations with various behavioral changes are not as significant as we might think.

However, the most recent publication on this subject sounds the alarm again. Scientists used comprehensive systems analysis to look at the range of biomarkers generated by various parasites and to assess their impact in a large cohort of subjects. The data point to a correlation between toxoplasmosis and several neurodegenerative conditions including Alzheimer’s and Parkinson’s disease. The T. gandii infection was also positively correlated with epilepsy and a number of cancers. The scientists not only identified correlations, they also described the biochemical pathways that may actually lead to the increased risk of developing these conditions. They concluded that toxoplasmosis is a risk factor for many neurological disorders, and thus this infection has to be taken into consideration when developing strategies for preventing or delaying the onset of various brain diseases.

Can something be done to cure or at least prevent T. gondii infection? Unfortunately, not much. There are no drugs or vaccines to treat this infection. There is a number of simple strategies to decrease the risk of infection among healthy people. They include avoiding the consumption of raw or undercooked meat (among humans, this is the most common way of getting infected), as well as general basic food handling safety practices.

References

Berdoy, M; Webster, J; Macdonald, D (2000) Fatal attraction in rats infected with Toxoplasma gondii. Proceedings of the Royal Society B: Biological Sciences. 267 (1452): 1591–1594. doi:10.1098/rspb.2000.1182.

Flegr, J (2007) Effects of Toxoplasma on Human Behavior. Schizophrenia Bulletin. 33 (3): 757–760. doi:10.1093/schbul/sbl074.

Flegr, J; Havlícek, J; Kodym, P; Malý, M; Smahel, Z (2002) Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. BMC Infectious Fiseases. 2: 11. doi:10.1186/1471-2334-2-11.

Kocazeybek, B; Oner, Y; Turksoy, R; Babur, C; Cakan, H; Sahip, N; Unal, A; Ozaslan, A; Kilic, S; Saribas, S; Aslan, M; Taylan, A; Koc, S; Dirican, A; Uner, H; Oz, V; Ertekin, C; Kucukbasmaci, O; Torun, M (2009) Higher prevalence of toxoplasmosis in victims of traffic accidents suggest increased risk of traffic accident in Toxoplasma-infected inhabitants of Istanbul and its suburbs. Forensic Science International. 187 (1–3): 103–108. doi:10.1016/j.forsciint.2009.03.007.

Torrey, EF; Bartko, JJ; Lun, ZR; Yolken, RH (2007) Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophrenia bulletin. 33 (3): 729–36. doi:10.1093/schbul/sbl050.

Arling, TA; Yolken, RH; Lapidus, M; Langenberg, P; Dickerson, FB; Zimmerman, SA; Balis, T; Cabassa, JA; Scrandis, DA; Tonelli, LH; Postolache, TT (2009) Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders. The Journal of Nervous and Mental Disease. 197 (12): 905–8. doi:10.1097/nmd.0b013e3181c29a23.

Sugden, K; Moffitt, TE; Pinto, L; Poulton, R; Williams, BS; Caspi, A (2016) Is Toxoplasma Gondii Infection Related to Brain and Behavior Impairments in Humans? Evidence from a Population-Representative Birth Cohort. PLOS ONE. 11 (2): e0148435. doi:10.1371/journal.pone.0148435.

Huân M. Ngô, Ying Zhou, Hernan Lorenzi, Kai Wang, Taek-Kyun Kim, Yong Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Seesandra V. Rajagopala, Craig W. Roberts, Fiona L. Henriquez, Alexandre Montpetit, Jenefer M. Blackwell, Sarra E. Jamieson, Kelsey Wheeler, Ian J. Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez, Roderick G. Davis, Liliana Soroceanu, Charles Cobbs, Dennis A. Steindler, Kenneth Boyer, A. Gwendolyn Noble, Charles N. Swisher, Peter T. Heydemann, Peter Rabiah, Shawn Withers, Patricia Soteropoulos, Leroy Hood, Rima McLeod. Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer. Scientific Reports, 2017; 7 (1) doi: 10.1038/s41598-017-10675-6

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