Saturday , November 28 2020

How the toxoplasmosis parasite transforms the synapses into the brain



About 30 to 50 percent of people have been infected with toxoplasma during their lifetime. In those over 50, you reach 50%. Toxoplasmosis usually goes unnoticed and those infected do not suspect that they are affected. Prof. Dr. Ildiko Rita Dunay, director of the OVGU's Institute for Inflammation and Neurodegeneration, explains: "In healthy people, the infection triggers short-term cold symptoms such as chills, fever, and body aches.In contrast, such infection can be dangerous for pregnant women or people with weakened immune systems.There is no therapy to get rid of the parasite when it attacks the brain.Then, once infected, it will last a lifetime. "

The parasite nests on the muscle tissue of infected animals, but not only: "Toxoplasma gondii is absorbed by humans through digestion, enters the bloodstream and also migrates to the brain where it remains in nerve cells," Dr. Med Karl-Heinz Smalla from the Special Molecular Biological Techniques Laboratory at LIN.

Magdeburg scientists have discovered in previous experiments with mice that there are surprising behavioral changes in animals infected with Toxoplasma gondii: "Rats, which are in fact cat fangs, have lost the natural fear of cats after infection. with the smell of cat urine, they still seemed to have developed a preference for cats, "the researchers said. Therefore, in order to explain these behavioral changes, they investigated changes in the brains of mice – in particular the molecular composition of the synapses, since these are the structures essential for the processing of signals in the brain.

In cooperation with the Helmholtz Center for Infection Research in Braunschweig, they were able to prove that, in a total of 300 synaptic proteins, levels in the brain following a toxoplasmosis infection had changed. In particular, proteins have been particularly reduced in the excitatory synapses that release glutamate. On the other hand, increased levels of proteins involved in immune responses were found.

For the treatment of toxoplasmosis infections, sulfadiazine, which partially inhibits the proliferation of Toxoplasms, is common. Psychiatrist and neuroscientist Björn Schott explains, "Now we wanted to find out how treatment with sulfadiazine affects the molecular changes in the brain caused by the infection." The result: the protein composition in the brains of the mice after treatment was comparable to that of uninfected co-specific ones. "All the proteins examined, responsible for the transmission of the glutamatergic signal, were again in the normal range, and the inflammatory activity also decreased measurably." The infection appears to increase the immune response, which reduces the proteins involved in glutamate-mediated synaptic excitation , while sulfadiazine reduces toxoplasmas, thus normalizing the immune response and causing synaptic protein recovery.

Even for humans, these findings may be medically relevant. "They support the suggestion that Toxoplasma gondii is a risk factor for neuropsychiatric disorders." Malfunctioning of glutamatergic synapses has been implicated in the causes of depression, schizophrenia, and autism. that immune responses can cause changes in synapses that can lead to neuropsychiatric disorders, "summarizes neuroimmunologist Dunay.

Original Publication:
DOI: 10.1186 / s12974-018-1242-1

idw 2018/11


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