Terrible! Parasites can manipulate the human brain!

June 6, 2019 / BIOON / - we are all different when we are sick Whether it's sneezing when we have a cold or biting when we have rabies, bacteria can change our behavior This is because bacteria need to travel from one host to another As a result, the behavior of the host often changes to help spread the pathogen For example, rabies can cause infected animals to attack people because the virus is spread through saliva But some microbes are more subtle Photo source: http://cn.bing.com Toxoplasma gondii parasite can only reproduce sexually in cats, but can infect any animal, hijack the brain and affect the behavior of the host In a series of events that made Charles Darwin laugh, rats and mice infected with Toxoplasma behaved in such a way that they could easily become prey to cats - that's where Toxoplasma wants to go Given that a third of the human brain also has Toxoplasma cysts, the ability of Toxoplasma to destroy the basic instinct of rodents is worrisome Toxoplasmosis, which lurks in humans, is associated with serious neurological diseases, including schizophrenia, intermittent rage and suicide, but has never been shown to be a direct cause Can parasites also manipulate humans? Is there a way to get rid of this parasite, and if so, will behavior return to normal? As a microbiologist, Bill Sullivan, Professor of pharmacology and toxicology at Indiana University, has studied Toxoplasma gondii for more than 20 years Not only has he found the parasite's effect on the host endlessly fascinating, but he has also been trying to identify its weaknesses so that doctors can better treat this incurable lifelong infection In collaboration with biochemist Ronald wek and neuroscientist Stephen L Boehm II, they have made an amazing discovery that parasites may not directly manipulate their rodent hosts On the contrary, the host's immune response to chronic infection may be the culprit Your brain is infected with Toxoplasma gondii, a single celled parasite that can travel all over the world - it has successfully infiltrated the brains of billions of creatures around the world, from birds to belugas However, of all species that Toxoplasma can infect, only cats can support its sexual phase After having sex in the cat's gut, Toxoplasma gondii is packaged as a solid egg sac, which is released into the environment through feces, and then can be ingested or inhaled by other animals Photo source: Toxoplasma gondii infection at http://cn.bing.com usually does not produce symptoms in humans unless their immune system is damaged, but the parasite will live as a latent tissue cyst in the body for a lifetime These tissue cysts are common in the brain, heart and skeletal muscle The formation of tissue cysts occurs in all infected animals, including many that end up on our plates Eating these tissue cysts in raw or undercooked meat can also spread infection Another way in which these tissue cysts act as vectors for parasites is by changing the behavior of the host Rats and mice with underlying toxoplasmosis became hyperactive, losing their instinctive fear of cats, essentially making them free lunches for cats J ennifer martynowicz, M.D., a student at Sullivan lab, is interested in the ability of latent toxoplasmosis to change behavior in mice It seems that this tiny microorganism is inert when it is wrapped in its tissue capsule wall, but how it does this has long been a mystery It is well known that Toxoplasma gondii releases a large number of parasite proteins to host cells, which can change gene activity, but how to transform them into changing behavior is still unclear Sullivan lab's previous work found that the FDA approved drug guannabenzine, used to treat hypertension, significantly reduced the number of brain cysts in infected mice called BALB / C Using the drug, martynowicz can solve a fundamental problem: if we reduce the number of parasitic cysts in the brain, can we return to normal behavior? Toxoplasma changes behavior - reversal of martynowicz's drug use for three weeks in mice with latent toxoplasmosis and hyperactivity When martynowicz examined the brains of the treated and non coronary mice, she found that the number of cysts in the treated mice decreased by 75%, reinforcing the results of previous studies In the first similar experiment, martynowicz studied whether the reduction of cysts affected the activity level of mice Happily, the hyperactivity normally seen in mice with latent toxoplasmosis has disappeared Animals treated with guanazelbenz behaved like normal, uninfected mice This suggests that their laboratory hypothesis is correct: brain cysts are related to behavioral changes In order to determine that this hyperactivity was caused by cysts, martynowicz decided to study the guanidine effect on another C57BL / 6 mouse strain that was more susceptible to Toxoplasma gondii infection Guanidine did not reduce the number of cysts in this mouse strain But it reversed hyperactivity These unexpected findings suggest that the hyperactivity of infected mice has nothing to do with the number of parasitic brain cysts To solve this confusing difference, martynowicz measured the levels of inflammation in the brains of these mice Other researchers have observed that parasitic cysts lurking in the brain attract immune cells and produce low levels of persistent inflammation Photo source: http://cn.bing.com does encephalitis change behavior? It is well known that guanazelbenz has anti-inflammatory effect Reducing brain inflammation seems to be exactly what these two infected mice do These results suggest that the hyperactivity of infected mice is more likely to be caused by their immune response than by parasite driven manipulation If so, the key to controlling some behavior changes of infected animals may be to regulate their immune response We don't know how neuroinflammation leads to hyperactivity But it's worth noting that some emerging studies have also found a link between inflammation and attention deficit hyperactivity disorder (ADHD) If our findings in mice, published in the Journal mbio, are extended to humans, they will have an important impact on how we currently treat brain infections Our results show that according to the immune response, brain infection may only have neurogenic effects on a small number of people Further research is needed to determine whether anti-inflammatory drugs such as guanazelbenz can effectively control these symptoms Reference: [1] is the brain sideline Toxoplasma manipulating your behavior, or is your immune system to blast? 【2】Jennifer Martynowicz et al Guanabenz Reverses a Key Behavioral Change Caused by Latent Toxoplasmosis in Mice by Reducing Neuroinflammation mBio DOI： 10.1128/mBio.00381-19 【3】Gretchen Hermes et al Neurological and behavioral abnormalities， ventricular dilatation， altered cellular functions， inflammation， and neuronal injury in brains of mice due to common， persistent， parasitic infection Journal of Neuroinflammation 20085：48 https：//doi.org/10.1186/1742-2094-5-48 【4】 Data and Statistics About ADHD 【5】Imaan Benmerzouga et al Guanabenz Repurposed as an Antiparasitic with Activity against Acute and Latent Toxoplasmosis Antimicrobial Agents and Chemotherapy DOI： 10.1128/AAC.01683-15 【6】Mohamed-Ali Hakimi et al Toxoplasma Effectors Targeting Host Signaling and Transcription Clinical Microbiology Reviews DOI：10.1128/CMR.00005-17 【7】Dolores E Hill et al Biology and epidemiology of Toxoplasma gondii in man and animals Animal Health Research Reviews DOI：https：//doi.org/10.1079/AHR2005100