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dc.contributor.authorLang, Daniel
dc.contributor.authorSchott, Björn H
dc.contributor.authorvan Ham, Marco
dc.contributor.authorMorton, Lorena
dc.contributor.authorKulikovskaja, Leonora
dc.contributor.authorHerrera-Molina, Rodrigo
dc.contributor.authorPielot, Rainer
dc.contributor.authorKlawonn, Frank
dc.contributor.authorMontag, Dirk
dc.contributor.authorJänsch, Lothar
dc.contributor.authorGundelfinger, Eckart D
dc.contributor.authorSmalla, Karl Heinz
dc.contributor.authorDunay, Ildiko Rita
dc.description.abstractChronic infection with the neurotropic parasite Toxoplasma gondii has been implicated in the risk for several neuropsychiatric disorders. The mechanisms, by which the parasite may alter neural function and behavior of the host, are not yet understood completely. Here, a novel proteomic approach using mass spectrometry was employed to investigate the alterations in synaptic protein composition in a murine model of chronic toxoplasmosis. In a candidate-based strategy, immunoblot analysis and immunohistochemistry were applied to investigate the expression levels of key synaptic proteins in glutamatergic signaling. A comparison of the synaptosomal protein composition revealed distinct changes upon infection, with multiple proteins such as EAAT2, Shank3, AMPA receptor, and NMDA receptor subunits being downregulated, whereas inflammation-related proteins showed an upregulation. Treatment with the antiparasitic agent sulfadiazine strongly reduced tachyzoite levels and diminished neuroinflammatory mediators. However, in both conditions, a significant number of latent cysts persisted in the brain. Conversely, infection-related alterations of key synaptic protein levels could be partly reversed by the treatment. These results provide evidence for profound changes especially in synaptic protein composition in T. gondii-infected mice with a downregulation of pivotal components of glutamatergic neurotransmission. Our results suggest that the detected synaptic alterations are a consequence of the distinct neuroinflammatory milieu caused by the neurotropic parasite.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.subjectChronic Toxoplasma infectionen_US
dc.subjectSynaptic proteinsen_US
dc.subjectToxoplasma gondiien_US
dc.titleChronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition.en_US
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en_US
dc.source.journaltitleJournal of neuroinflammation

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